Kesavan Shan - Academia.edu (original) (raw)

Papers by Kesavan Shan

Research paper thumbnail of Assessment of Myocardial Viability with Stress Echocardiography

Cardiology Clinics, Aug 1, 1999

Research paper thumbnail of Tumor necrosis factor-? and tumor necrosis factor receptors in human heart failure

Heart Failure Reviews, Nov 1, 1996

The basic mechanisms that are responsible for the development and progression of congestive heart... more The basic mechanisms that are responsible for the development and progression of congestive heart failure are not known. Although clinicians have traditionally viewed heart failure as a hemodynamic disorder related to left ventricular pump dysfunction, one of the more recent concepts that has emerged is that the development and progression of heart failure is attributable, at least in part, to the overexpression of biologically active molecules that can contribute both to patient symptomatology as well as to disease progression. In this regard, one of the more recent interesting and intriguing observations in clinical heart failure research is the finding that a proinflammatory cytokine, termed tumor necrosis factor-c~ (TNF-c0, is expressed in patients with heart failure. Accordingly, the focns of the present brief review is to summarize recent clinical and experimental observations that implicate the elaboration of TNF-~ and TNF receptors in the progression of human heart failure.

Research paper thumbnail of Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery

The online version of this article, along with updated information and services, is located on the

Research paper thumbnail of Viability Role of Cardiac Magnetic Resonance Imaging in the Assessment of Myocardial

Research paper thumbnail of Tumor necrosis factor-a and tumor necrosis factor receptors in human heart failure

Research paper thumbnail of Assessment of Myocardial Viability with Stress Echocardiography

Research paper thumbnail of and beta-adrenergic receptor density in humans Relation of tissue Doppler derived myocardial velocities to myocardial structure

Research paper thumbnail of Active interstitial remodeling: an important process in the hibernating human myocardium

Journal of the American College of Cardiology, 2002

The purpose of this study is to investigate the morphologic characteristics of the cardiac inters... more The purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery. BACKGROUND Myocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium. METHODS We evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 (201 Tl) tomography before coronary bypass surgery. During surgery, transmural myocardial biopsies were performed guided by transesophageal echocardiography. Myocardial biopsies were stained immunohistochemically to investigate fibroblast phenotype and examine evidence of active remodeling in the heart. RESULTS Among the 29 biopsied segments included in the study, 24 showed evidence of systolic dysfunction. The majority of dysfunctional segments (86.4%) were viable (201 Tl uptake Ն60%). After revascularization, 12 dysfunctional segments recovered function as assessed with an echocardiogram three months after bypass surgery. Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin heavy chain (SMemb) were noted in dysfunctional segments, predominantly located in border areas adjacent to viable myocardial tissue. Segments with recovery had higher SMemb expression (0.46 Ϯ 0.16% [n ϭ 12] vs. 0.10 Ϯ 0.02% [n ϭ 12]; p Ͻ 0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 Ϯ 0.026 [n ϭ 12] vs. 0.07 Ϯ 0.01 [n ϭ 12]; p Ͻ 0.05) compared with segments without recovery, indicating fibroblast activation and higher cellularity of the fibrotic areas. In addition, interstitial deposition of the matricellular protein tenascin, a marker of active remodeling, was higher in hibernating segments than in segments with persistent dysfunction (p Ͻ 0.05), suggesting an active continuous fibrotic process. Multiple logistic regression demonstrated a significant independent association between SMemb expression and functional recovery (p Ͻ 0.01). CONCLUSIONS Fibroblast activation and expression of SMemb and tenascin provide evidence of continuous remodeling in the cardiac interstitium of the hibernating myocardium, an important predictor of recovery of function after revascularization.

Research paper thumbnail of Basic mechanisms in heart failure: The cytokine hypothesis

Journal of Cardiac Failure, 1996

Research paper thumbnail of Tumor necrosis factor-? and tumor necrosis factor receptors in human heart failure

Heart Failure Reviews, 1996

The basic mechanisms that are responsible for the development and progression of congestive heart... more The basic mechanisms that are responsible for the development and progression of congestive heart failure are not known. Although clinicians have traditionally viewed heart failure as a hemodynamic disorder related to left ventricular pump dysfunction, one of the more recent concepts that has emerged is that the development and progression of heart failure is attributable, at least in part, to the overexpression of biologically active molecules that can contribute both to patient symptomatology as well as to disease progression. In this regard, one of the more recent interesting and intriguing observations in clinical heart failure research is the finding that a proinflammatory cytokine, termed tumor necrosis factor-c~ (TNF-c0, is expressed in patients with heart failure. Accordingly, the focns of the present brief review is to summarize recent clinical and experimental observations that implicate the elaboration of TNF-~ and TNF receptors in the progression of human heart failure.

Research paper thumbnail of The role of cytokines in disease progression in heart failure

Current Opinion in Cardiology, 1997

Research paper thumbnail of Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery Disease and Left Ventricular Dysfunction

Circulation, 2002

Background— Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viabi... more Background— Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. Methods and Results— MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (β) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (<100 μm) density, capillary density and area, arteriolar and venular density, and percent collagen content were quantitated with immunohistochemistry. Peak MCI correlated with microvascular density ( r =0.59, P <0.001) and capilla...

Research paper thumbnail of Role of Cardiac Magnetic Resonance Imaging in the Assessment of Myocardial Viability

Research paper thumbnail of Identification of Hibernating Myocardium With Quantitative Intravenous Myocardial Contrast Echocardiography

Circulation, 2003

Background— There are currently no data on the accuracy of intravenous myocardial contrast echoca... more Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl 201 ) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl 201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with ...

Research paper thumbnail of Altered Adrenergic Receptor Density in Myocardial Hibernation in Humans

Circulation, 2000

Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial... more Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. Methods and Results —Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. α- and β-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compar...

Research paper thumbnail of Deceleration Time in Ischemic Cardiomyopathy

Circulation, 2001

Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunctio... more Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. Methods and Results —Forty patients with ischemic cardiomyopathy underwent 201 Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 μg · kg −1 · min −1 ) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE ( r =0.72), scar perfusion defect by SPECT ( r =−0.69), and the change in ejection fraction (ΔEF) after surgery ( r =0.77) (all P <0.01). DT >150 ms effectively identified (sensitivity 79%, specificity 81%) patients with ΔEF ≥5%. The population was divided into 2 groups according to DT: group 1 (DT >150 ms, n=21) and gr...

Research paper thumbnail of Evidence for an Active Inflammatory Process in the Hibernating Human Myocardium

The American Journal of Pathology, 2002

Research paper thumbnail of Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting

The American Journal of Cardiology, 2002

We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels... more We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide (NOS2) in humans. Seven patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsies (2 biopsies per patient for a total of 14 specimens) at the time of bypass surgery. The specimens were analyzed for the number of mRNA copies of TNF-alpha and NOS2. In addition, serum levels of TNF-alpha and nitrite were determined before and after surgery. Normal segments (n = 7) had fewer numbers of mRNA copies of both TNF-alpha (54.6 vs 6.5, p = 0.002) and NOS2 (3,093 +/- 486 vs 661 +/- 259, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) than dysfunctional segments (n = 7). Peak systolic velocity (Sm) (13.3 +/- 1.4 vs 4.9 +/- 1.6 cm/s, p = 0.002) and early diastolic velocity (Em) (16.5 +/- 2.7 vs 8.8 +/- 1.3 cm/s, p = 0.02) were significantly higher in normal segments. A significant correlation was present among Em, Sm, and the number of mRNA copies of TNF-alpha and NOS2 at baseline and during infusion of dobutamine (r range -0.72 to -0.92, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 for all). Likewise, significant relations were present between the changes in serum cytokine levels and changes in the mitral annulus diastolic velocity, E/Ea ratio, and end-diastolic wall stress (r range 0.75 to 0.88, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;/=0.05 for all). In conclusion, Sm and Em are strongly dependent on the regional levels of cytokine gene expression, which are known to have negative inotropic and lusitropic effects when overexpressed.

Research paper thumbnail of Role of MRI in clinical cardiology

The Lancet, 2004

Rapid progress has been made in cardiac MRI (CMRI) over the past decade, which has firmly establi... more Rapid progress has been made in cardiac MRI (CMRI) over the past decade, which has firmly established it as a reliable and clinically important technique for assessment of cardiac structure, function, perfusion, and myocardial viability. Its versatility and accuracy is unmatched by any other individual imaging modality. CMRI is non-invasive and has high spatial resolution and avoids use of potentially nephrotoxic contrast agent or radiation. It has been extensively studied against other established non-invasive imaging modalities and has been shown to be superior in many scenarios, particularly with respect to assessment of cardiac and great vessel morphology and left ventricular function. Furthermore, its clinical use continues to expand with increasing experience and proliferation of CMRI centres. As worldwide prevalence of cardiovascular disease continues to rise, CMRI provides opportunity for improved and cost-effective non-invasive assessment. Continued progress in CMRI technology promises to further widen its clinical application in coronary imaging, myocardial perfusion, comprehensive assessment of valves, and plaque characterisation.

Research paper thumbnail of Assessment of Myocardial Viability with Stress Echocardiography

Cardiology Clinics, Aug 1, 1999

Research paper thumbnail of Tumor necrosis factor-? and tumor necrosis factor receptors in human heart failure

Heart Failure Reviews, Nov 1, 1996

The basic mechanisms that are responsible for the development and progression of congestive heart... more The basic mechanisms that are responsible for the development and progression of congestive heart failure are not known. Although clinicians have traditionally viewed heart failure as a hemodynamic disorder related to left ventricular pump dysfunction, one of the more recent concepts that has emerged is that the development and progression of heart failure is attributable, at least in part, to the overexpression of biologically active molecules that can contribute both to patient symptomatology as well as to disease progression. In this regard, one of the more recent interesting and intriguing observations in clinical heart failure research is the finding that a proinflammatory cytokine, termed tumor necrosis factor-c~ (TNF-c0, is expressed in patients with heart failure. Accordingly, the focns of the present brief review is to summarize recent clinical and experimental observations that implicate the elaboration of TNF-~ and TNF receptors in the progression of human heart failure.

Research paper thumbnail of Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery

The online version of this article, along with updated information and services, is located on the

Research paper thumbnail of Viability Role of Cardiac Magnetic Resonance Imaging in the Assessment of Myocardial

Research paper thumbnail of Tumor necrosis factor-a and tumor necrosis factor receptors in human heart failure

Research paper thumbnail of Assessment of Myocardial Viability with Stress Echocardiography

Research paper thumbnail of and beta-adrenergic receptor density in humans Relation of tissue Doppler derived myocardial velocities to myocardial structure

Research paper thumbnail of Active interstitial remodeling: an important process in the hibernating human myocardium

Journal of the American College of Cardiology, 2002

The purpose of this study is to investigate the morphologic characteristics of the cardiac inters... more The purpose of this study is to investigate the morphologic characteristics of the cardiac interstitium in the hibernating human myocardium and evaluate whether active remodeling is present and is an important determinant of functional recovery. BACKGROUND Myocardial hibernation is associated with structural myocardial changes, which involve both the cardiomyocytes and the cardiac interstitium. METHODS We evaluated 15 patients with coronary disease with two-dimensional echocardiography and thallium-201 (201 Tl) tomography before coronary bypass surgery. During surgery, transmural myocardial biopsies were performed guided by transesophageal echocardiography. Myocardial biopsies were stained immunohistochemically to investigate fibroblast phenotype and examine evidence of active remodeling in the heart. RESULTS Among the 29 biopsied segments included in the study, 24 showed evidence of systolic dysfunction. The majority of dysfunctional segments (86.4%) were viable (201 Tl uptake Ն60%). After revascularization, 12 dysfunctional segments recovered function as assessed with an echocardiogram three months after bypass surgery. Interstitial fibroblasts expressing the embryonal isoform of smooth muscle myosin heavy chain (SMemb) were noted in dysfunctional segments, predominantly located in border areas adjacent to viable myocardial tissue. Segments with recovery had higher SMemb expression (0.46 Ϯ 0.16% [n ϭ 12] vs. 0.10 Ϯ 0.02% [n ϭ 12]; p Ͻ 0.05) and a higher ratio of alpha-smooth muscle actin to collagen (0.14 Ϯ 0.026 [n ϭ 12] vs. 0.07 Ϯ 0.01 [n ϭ 12]; p Ͻ 0.05) compared with segments without recovery, indicating fibroblast activation and higher cellularity of the fibrotic areas. In addition, interstitial deposition of the matricellular protein tenascin, a marker of active remodeling, was higher in hibernating segments than in segments with persistent dysfunction (p Ͻ 0.05), suggesting an active continuous fibrotic process. Multiple logistic regression demonstrated a significant independent association between SMemb expression and functional recovery (p Ͻ 0.01). CONCLUSIONS Fibroblast activation and expression of SMemb and tenascin provide evidence of continuous remodeling in the cardiac interstitium of the hibernating myocardium, an important predictor of recovery of function after revascularization.

Research paper thumbnail of Basic mechanisms in heart failure: The cytokine hypothesis

Journal of Cardiac Failure, 1996

Research paper thumbnail of Tumor necrosis factor-? and tumor necrosis factor receptors in human heart failure

Heart Failure Reviews, 1996

The basic mechanisms that are responsible for the development and progression of congestive heart... more The basic mechanisms that are responsible for the development and progression of congestive heart failure are not known. Although clinicians have traditionally viewed heart failure as a hemodynamic disorder related to left ventricular pump dysfunction, one of the more recent concepts that has emerged is that the development and progression of heart failure is attributable, at least in part, to the overexpression of biologically active molecules that can contribute both to patient symptomatology as well as to disease progression. In this regard, one of the more recent interesting and intriguing observations in clinical heart failure research is the finding that a proinflammatory cytokine, termed tumor necrosis factor-c~ (TNF-c0, is expressed in patients with heart failure. Accordingly, the focns of the present brief review is to summarize recent clinical and experimental observations that implicate the elaboration of TNF-~ and TNF receptors in the progression of human heart failure.

Research paper thumbnail of The role of cytokines in disease progression in heart failure

Current Opinion in Cardiology, 1997

Research paper thumbnail of Microvascular Structural Correlates of Myocardial Contrast Echocardiography in Patients With Coronary Artery Disease and Left Ventricular Dysfunction

Circulation, 2002

Background— Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viabi... more Background— Myocardial contrast echocardiography (MCE) has been used to evaluate myocardial viability. There are no data, however, on the pathological determinants of myocardial perfusion by MCE in humans and the implications of such determinants. Methods and Results— MCE was performed in 20 patients with coronary artery disease and ventricular dysfunction within 24 hours before myocardial biopsy at surgery using a continuous Optison infusion (12 to 16 cc/h), with intermittent pulse inversion harmonics and incremental triggering. Peak myocardial contrast intensity (MCI) and the rate of increase in MCI (β) were quantitated. Thirty-six transmural myocardial biopsies (2 per patient) were obtained by transesophageal echocardiography. Total microvascular (<100 μm) density, capillary density and area, arteriolar and venular density, and percent collagen content were quantitated with immunohistochemistry. Peak MCI correlated with microvascular density ( r =0.59, P <0.001) and capilla...

Research paper thumbnail of Role of Cardiac Magnetic Resonance Imaging in the Assessment of Myocardial Viability

Research paper thumbnail of Identification of Hibernating Myocardium With Quantitative Intravenous Myocardial Contrast Echocardiography

Circulation, 2003

Background— There are currently no data on the accuracy of intravenous myocardial contrast echoca... more Background— There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl 201 ) scintigraphy. Methods and Results— Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl 201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with ...

Research paper thumbnail of Altered Adrenergic Receptor Density in Myocardial Hibernation in Humans

Circulation, 2000

Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial... more Background —Alterations in adrenergic receptor densities can potentially contribute to myocardial dysfunction. Their relevance to myocardial hibernation in humans is unknown. Methods and Results —Accordingly, 22 transmural myocardial biopsies were obtained in 11 patients with ischemic ventricular dysfunction during bypass surgery, guided by transesophageal echocardiography. Patients underwent dobutamine echocardiography (DE) and rest scintigraphic studies before revascularization and DE at 3 to 4 months. α- and β-receptor density (ARD and BRD) and extent of fibrosis were quantified from the myocardial biopsies. Of the 22 segments, 16 had abnormal rest function and 6 were normal. Severely hypokinetic or akinetic segments showed a 2.4-fold increase in ARD with a concomitant 50% decrease in BRD compared with normal segments. An increase in ARD, a decrease in BRD to a lesser extent, and thus an increase in ARD/BRD ratio were seen in dysfunctional segments with contractile reserve compar...

Research paper thumbnail of Deceleration Time in Ischemic Cardiomyopathy

Circulation, 2001

Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunctio... more Background —In patients with heart failure secondary to left ventricular (LV) systolic dysfunction, a short deceleration time (DT) successfully predicts clinical outcome. The impact of myocardial viability and revascularization on the mitral inflow velocities, however, is unknown. Methods and Results —Forty patients with ischemic cardiomyopathy underwent 201 Tl scintigraphy (SPECT) and 2D, Doppler, and dobutamine echocardiography (DE, to 40 μg · kg −1 · min −1 ) 2 days before CABG. Echocardiography was repeated 3 months after revascularization to determine recovery of function. Significant correlations were present between DT and LV contractile reserve by DE ( r =0.72), scar perfusion defect by SPECT ( r =−0.69), and the change in ejection fraction (ΔEF) after surgery ( r =0.77) (all P <0.01). DT >150 ms effectively identified (sensitivity 79%, specificity 81%) patients with ΔEF ≥5%. The population was divided into 2 groups according to DT: group 1 (DT >150 ms, n=21) and gr...

Research paper thumbnail of Evidence for an Active Inflammatory Process in the Hibernating Human Myocardium

The American Journal of Pathology, 2002

Research paper thumbnail of Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting

The American Journal of Cardiology, 2002

We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels... more We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide (NOS2) in humans. Seven patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsies (2 biopsies per patient for a total of 14 specimens) at the time of bypass surgery. The specimens were analyzed for the number of mRNA copies of TNF-alpha and NOS2. In addition, serum levels of TNF-alpha and nitrite were determined before and after surgery. Normal segments (n = 7) had fewer numbers of mRNA copies of both TNF-alpha (54.6 vs 6.5, p = 0.002) and NOS2 (3,093 +/- 486 vs 661 +/- 259, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) than dysfunctional segments (n = 7). Peak systolic velocity (Sm) (13.3 +/- 1.4 vs 4.9 +/- 1.6 cm/s, p = 0.002) and early diastolic velocity (Em) (16.5 +/- 2.7 vs 8.8 +/- 1.3 cm/s, p = 0.02) were significantly higher in normal segments. A significant correlation was present among Em, Sm, and the number of mRNA copies of TNF-alpha and NOS2 at baseline and during infusion of dobutamine (r range -0.72 to -0.92, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 for all). Likewise, significant relations were present between the changes in serum cytokine levels and changes in the mitral annulus diastolic velocity, E/Ea ratio, and end-diastolic wall stress (r range 0.75 to 0.88, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;/=0.05 for all). In conclusion, Sm and Em are strongly dependent on the regional levels of cytokine gene expression, which are known to have negative inotropic and lusitropic effects when overexpressed.

Research paper thumbnail of Role of MRI in clinical cardiology

The Lancet, 2004

Rapid progress has been made in cardiac MRI (CMRI) over the past decade, which has firmly establi... more Rapid progress has been made in cardiac MRI (CMRI) over the past decade, which has firmly established it as a reliable and clinically important technique for assessment of cardiac structure, function, perfusion, and myocardial viability. Its versatility and accuracy is unmatched by any other individual imaging modality. CMRI is non-invasive and has high spatial resolution and avoids use of potentially nephrotoxic contrast agent or radiation. It has been extensively studied against other established non-invasive imaging modalities and has been shown to be superior in many scenarios, particularly with respect to assessment of cardiac and great vessel morphology and left ventricular function. Furthermore, its clinical use continues to expand with increasing experience and proliferation of CMRI centres. As worldwide prevalence of cardiovascular disease continues to rise, CMRI provides opportunity for improved and cost-effective non-invasive assessment. Continued progress in CMRI technology promises to further widen its clinical application in coronary imaging, myocardial perfusion, comprehensive assessment of valves, and plaque characterisation.