Michael Jeserich

Vitamin C Improves Endothelial Dysfunction of Epicardial Coronary Arteries in Hypertensive Patients

BACKGROUND There is evidence for increased formation of free radicals in patients with hypertension, raising the possibility that NO is inactivated by free radicals, which impairs coronary endothelial function. Therefore, we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension. METHODS AND RESULTS In 22 hypertensive patients without relevant coronary artery stenoses, endothelium-dependent vascular responses of the left anterior descending coronary artery (LAD) to acetylcholine (0.01, 0.1, and 1.0 micromol/L) were determined before and immediately after intravenous infusion of 3 g vitamin C (17 patients) or placebo (5 patients). In a subgroup of 10 patients, papaverine-induced flow-dependent vasodilation (FDD) was measured before and after vitamin C (5 patients) or placebo (5 patients) infusion. Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography. Before vitamin C infusion, the mean changes of LAD luminal areas at increasing doses of acetylcholine were -6.1+/-2.2%, -15.2+/-4.9%, and -33.9+/-8.1% (negative numbers symbolize vasoconstriction) and during FDD, 5.4+/-1.0%. The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion, LAD luminal areas changed by -3.2+/-2.3%, -5.8+/-3.6%, and -10.2+/-5.6% (P<.05, acetylcholine) and 17.8+/-2.8% (P<.05, FDD). Doppler flow velocity (during baseline, acetylcholine, and FDD) was not significantly affected by vitamin C. CONCLUSIONS Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients.

Effect of chronic angiotensin-converting enzyme inhibition on endothelial function in patients with chronic heart failure

Chronic heart failure is associated with neurohumoral activation and alterations of the peripheral circulation and skeletal muscle. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data suggest an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure and may be involved in the impaired reactive hyperemia in these patients. In conductance vessels, flow-dependent dilation and the nitroglycerin-induced dilator response is attenuated in congestive heart failure as compared to normal subjects, indicating both endothelial dysfunction and a defect of smooth muscle relaxation. Recent data suggest that angiotensin-converting enzyme (ACE) inhibitors can improve endothelial function of resistance vessels, reduce serum level of the soluble endothelial (vascular cell) adhesion molecule (VCAM-1) and, in addition, improve peripheral vascular function by reducing or limiting the influence of cyclo-oxygenase-dependent vasoconstricting factor(s). It is conceivable that these beneficial effects of chronic ACE inhibition are due, in part, to blockade of bradykinin degradation by the ACE and the increased endothelial synthesis of prostaglandins and/or the release of nitric oxide by enhanced tissue levels of bradykinin.

Coronary Vasoregulation in Patients With Various Risk Factors in Response to Cold Pressor Testing Contrasting Myocardial Blood Flow Responses to Short- and Long-Term Vitamin C Administration

OBJECTIVES We sought to determine whether abnormal myocardial blood flow (MBF) responses to the cold pressor test (CPT) in patients with various risk factors may involve different mechanisms that could lead to varying responses of short- and long-term administration of antioxidants. BACKGROUND There is a growing body of evidence that increased vascular production of reactive oxygen species markedly reduces the bioavailability of endothelium-derived nitric oxide, leading to impaired vasodilator function. It is unknown whether increased oxidative stress is the prevalent mechanism underlying endothelial dysfunction in patients with different coronary risk factors. METHODS Fifty patients with normal coronary angiograms were studied. The MBF responses to CPT was determined by means of positron emission tomography before and after intravenous infusion of 3 g vitamin C or saline (placebo), as well as after 3 months and 2 years of 2 g vitamin C or placebo supplementation daily. RESULTS In hypertensive patients, the change in MBF (DeltaMBF) was not modified significantly by short-term vitamin C administration challenges (0.20 +/- 0.20 ml/g/min; p = NS) but was significantly increased after three months and two years of treatment with vitamin C versus baseline (0.58 +/- 0.27 and 0.63 +/- 0.17 vs. 0.14 +/- 0.18 ml/g/min; both p < or = 0.001). In smokers, DeltaMBF in response to CPT was significantly increased after short-term vitamin C infusion and long-term vitamin C treatment (0.52 +/- 0.10, 0.54 +/- 0.13, 0.50 +/- 0.07 vs. -0.08 +/- 0.10 ml/g/min; all p < or = 0.001). In hypercholesterolemic patients, no improvement in DeltaMBF during CPT was observed after short- and long-term vitamin C treatment (0.05 +/- 0.14, 0.08 +/- 0.18, 0.02 +/- 0.19 vs. 0.08 +/- 0.16 ml/g/min; p = NS). The CPT-induced DeltaMBF in hypertensive patients and smokers after follow-up was significant as compared with placebo and control subjects (p < or = 0.001). CONCLUSIONS The present study revealed marked heterogeneous responses in MBF changes to short- and long-term vitamin C treatment in patients with various risk factors, which highlights the quite complex nature underlying abnormal coronary vasomotion.

Fusion imaging: Combined visualization of 3D reconstructed coronary artery tree and 3D myocardial scintigraphic image in coronary artery disease

Background: In patients with coronary artery disease, coronary angiography is performed for assessment of epicardial coronary artery stenoses. In addition, myocardial scintigraphy is commonly used to evaluate regional myocardial perfusion. These two-dimensional (2D) imaging modalities are typically reviewed through a subjective, visual observation by a physician. Even though on the analysis of 2D display scintigraphic myocardial perfusion segments are arbitrarily assigned to three major coronary artery systems, the standard myocardial distribution territories of the coronary tree correspond only in 50–60% of patients. On the other hand, the mental integration of both 2D images of coronary angiography and myocardial scintigraphy does not allow an accurate assignment of particular myocardial perfusion regions to the corresponding vessels. To achieve an objective assignment of each vessel segment of the coronary artery tree to the corresponding myocardial regions, we have developed a 3D ‘fusion image’ technique and applied it to patients with coronary artery disease. The morphological data (coronary angiography) and perfusion data (myocardial scintigraphy) are displayed in a 3D format, and these two 3D data sets are merged into one 3D image. Results: Seventy-eight patients with coronary artery disease were studied with this new 3D fusion technique. Of 162 significant coronary lesions, 120 (74%) showed good coincidence with regional myocardial perfusion abnormality on 3D fusion image. No regional myocardial perfusion abnormality was found in 44 (26%) lesions. Furthermore, the 3D fusion image revealed 24 ischemic myocardial regions that could not be related to angiographically significant coronary artery lesions. Conclusion: The results of this study demonstrate that our newly developed 3D fusion technique is useful for an accurate assignment of coronary vessel segments to the corresponding myocardial perfusion regions, and suggest that it may be helpful to improve the interpretative and decision-making process in the treatment of patients with coronary artery disease.

Non-invasive imaging in the diagnosis of acute viral myocarditis

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail.Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail.

3D Assessment of myocardial perfusion parameter combined with 3D reconstructed coronary artery tree from digital coronary angiograms

In patients with coronary artery disease coronary angiography plays an important role in the clinical decision-making process. However, it has been recognized that no simple relation exists between the visually or quantitatively evaluated severity of coronary artery stenoses and its effects on regional myocardial perfusion. This paper describes for the first time the development and application of a 3D technique that visualizes and quantifies regional myocardial perfusion parameters from biplane coronary angiograms by using the impulse response analysis technique. The 3D reconstructed coronary tree is automatically superimposed on the 3D perfusion image to generate and visualize an ‘integrated’ 3D image. The preliminary results in patients with critical coronary artery stenoses indicate that our combined 3D fusion image provides flow information from the major coronary arteries. This 3D fusion image may provide useful information in the management of patients with coronary artery disease.

Effect of Ascorbic Acid on Endothelial Dysfunction of Epicardial Coronary Arteries in Chronic Smokers Assessed by Cold Pressor Testing

Background: In chronic smokers there is evidence for increased formation of oxygen-derived free radicals within the vessel wall impairing endothelial function. It has been suggested that the inactivation of endothelium-derived nitric oxide by oxygen free radicals contributes to endothelial dysfunction. Hence, we tested the hypothesis that in chronic smokers the antioxidant ascorbic acid could improve abnormal endothelial function of epicardial coronary arteries. Methods and Results: Thirty-one patients (mean age 57 ± 9 years) referred for routine diagnostic catheterization for evaluation of chest pain and without angiographically significant coronary artery stenoses were randomly assigned to one of the study groups to assess vasomotor response of epicardial coronary arteries due to cold pressor testing (CPT) before and after intravenous infusion of 3 g of ascorbic acid or 100 ml × 0.9% saline infusion. In 6 controls (mean age 55 ± 3 years) CPT led to a similar increase in luminal area before and after ascorbic acid administration (26.5 ± 15.0 vs. 28.4 ± 17.7%, p = NS). In 15 chronic smokers (mean age 55 ± 9 years), CPT induced a decrease in the luminal area of –18.5 ± 6.3%. This flow-dependent vasoconstriction was significantly reversed to 7.7 ± 6.2% (p ≤ 0.03) vasodilation after intravenous ascorbic acid administration. In 10 chronic smokers (mean age 57 ± 11 years) saline infusion (placebo) did not have a significant effect on CPT-induced vasoconstriction (–12.7 ± 5.1 vs. –13.1 ± 5.1%, p = NS). The CPT-induced increase in luminal area in chronic smokers after ascorbic acid infusion was significant compared to controls and placebo (each p ≤ 0.05). Our assessment of endothelium-independent responses to nitroglycerin revealed no significant differences between the single study groups (p = NS). Conclusion: In chronic smokers acute intravenous administration of ascorbic acid significantly improves CPT-induced coronary endothelium-dependent dysfunction. According to the current understanding, this effect is due to improved cellular redox imbalance and prevention of nitric oxide inactivation in the endothelium and subendothelial space.

The athlete’s heart Part I (Review)

Importance of the athletes heart has been arisen in the last decades. Consequences of the sedentary way of life are the most threatening through the impairments of the cardiovascular system. Endurance performance is mostly limited by the characteristics of the athletes heart. Sudden death of the athletes is always associated with cardiac disorders. Main characteristics of the athletes heart can be divided into morphologic, functional and regulatory ones. The main morphologic characteristics are the physiologic left ventricular (LV) hypertrophy and a richer coronary capillary network. The functional adaptation contains a better systolic and diastolic function, modified metabolism and electric characteristics. The most easily detected modification is the better LV diastolic function. Adaptation of the cardiac regulation is manifested mostly by a lower heart rate (HR). Summarizing: the athletes heart is an enlarged but otherwise normal heart characterized by a low heart rate, an increased pumping capacity, and a greater ability to deliver oxygen to skeletal muscle.

Absence of vascular tolerance in conductance vessels after 48 hours of intravenous nitroglycerin in patients with coronary artery disease.

OBJECTIVES We examined whether reflex neurohormonal constrictor forces attenuate the vasodilator action of nitroglycerin on large peripheral conductance vessels. BACKGROUND Continuous nitroglycerin therapy is associated with the development of early tolerance with respect to its hemodynamic effects. It remains to be demonstrated whether vascular tolerance of large conductance vessels is an important contributory factor. METHODS Radial artery diameter and forearm blood flow velocity were measured before and 24 and 48 h after continuous intravenous nitroglycerin infusion (0.5 microgram/kg body weight per min) in 10 patients with coronary artery disease (mean age +/- SEM 59 +/- 4 years) by using a high resolution ultrasound device. Blood flow (ml/min) was calculated from mean blood flow velocity and cross-sectional area. RESULTS Increasing concentrations of nitroglycerin led to a dose-dependent increase in radial artery diameter (maximal +24 +/- 2%) and heart rate. Forearm vascular resistance and forearm blood flow were unchanged. After 24 and 48 h of treatment, additional nitroglycerin did not further increase radial artery diameter, indicating that the nitroglycerin-induced dilation of the radial artery was maintained and was still maximal. In addition, radial artery diameter measured before and after 48 h of nitroglycerin infusion and after withdrawal of nitroglycerin in five additional patients showed that, after withdrawal, arterial diameter returned to baseline values within 35 min. Plasma renin activity and serum aldosterone and vasopressin levels increased significantly at 24 and 48 h, accompanied by a decrease in hematocrit. CONCLUSIONS Continuous intravenous administration of nitroglycerin exerts a sustained vasodilator effect for 48 h in large conductance vessels. Neurohormonal activation and compensatory intravascular volume expansion do not attenuate the vasodilator effects of nitroglycerin on peripheral conductance vessels during the 1st 48 h of treatment.

Evidence of Myocardial Edema in Patients With Nonischemic Dilated Cardiomyopathy

Nonischemic dilated cardiomyopathy (DCM) is associated with high mortality and morbidity. Cardiovascular magnetic resonance allows for the noninvasive assessment of function, morphology, and myocardial edema. Activation of inflammatory pathways may play an important role in the etiology of chronic DCM and may also be involved in the disease progression.