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Cardiac hemodynamics, coronary circulation and interventional cardiology.

Microcirculation is the functional end of the coronary circulation and it plays a key role in the regulation of coronary blood flow, both on the local and global scales. A good understanding of its function under physiological and pathophysiological conditions is crucial but, because of its micro-scale, access to this part of the coronary circulation is extremely difficult and requires a considerable amount of innovation and new technologies. Dynamics of the coronary circulation provide the true vehicle by which blood supply reaches the myocardium- coronary vasculature is only the conducting component of that vehicle. It is highly unlikely that the pulsatile nature of the flow, the capacitance of the conducting vessels and the constant pounding of coronary vasculature by surrounding tissue are not part of the design, regulation, and function of the coronary circulation. Interventions, whether to assess or to correct coronary stenosis, continue to be the main clinical avenue to dealing with coronary heart disease. Clinical decisions rely heavily on the ability to determine the true morphology of an occlusive lesion, to predict the future course of that lesion and to assess the functional toll on coronary blood supply which it will inflict at each stage.

Animals↗

[Regulation of coronary circulation].

In the submitted review the author deals with specific features of the coronary circulation, coronary reserve and importance of regulation of the tonus of the coronary arteries at their epicardiac course and the tonus at the arteriolar level. In the subsequent part the author deals systematically first with the nervous regulation incl. the basic importance of the alpha-adrenergic (vasoconstrictor) and beta-adrenergic (vaso-dilating) sympathomimetic component. He mentions also the importance of neuropeptides (neuropeptide Y and substance P). Attention is devoted to the importance of the endothelium and endothelial vasoactive substances in the control of circulation. The main representatives of substances with a vasodilatating action are the endothelial relaxation factor and prostacycline, as to vasoconstrictor substances it is endothelin, thromboxan A2 and some growth factors. The authors discuss also the mechanical component, i. e. the influence of the blood flow and viscosity on the tonus of the coronary arteries. Finally the author draws attention to the clinical importance of disorders of regulatory mechanism in atherosclerosis and some clinical entities.

Coronary Circulation↗

Beta-thromboglobulin release within coronary circulation--a potential role of platelets in ergonovine-induced coronary vasospasm.

The role of platelets in the pathogenesis of acute myocardial ischemia is not yet agreed upon. In this study, the gradient of plasma beta-thromboglobulin concentration between coronary sinus and aorta was used as an indicator of platelet activation within the coronary circulation. Blood samples were drawn before and after injection of ergonovine maleate in patients without fixed coronary stenosis in whom significant coronary spasm was induced by ergonovine (n = 8, Group 1), patients with significant stenosis (greater than or equal to 75%) of the left anterior descending artery and positive ergonovine test (n = 7, Group 2) and patients with significant stenosis of left anterior descending coronary artery and negative ergonovine test (n = 11, Group 3). Fifteen patients with normal coronary arteries who were negative in the ergonovine test served as controls (Group 4). After the ergonovine test, all Group 1 patients revealed a significant increase of beta-thromboglobulin gradient (P less than 0.001), while those in other groups did not. Additionally, the gradient after the ergonovine test of Group 1 patients was larger than those of the other groups (P less than 0.01). All blood samples after the ergonovine test were collected before or at the onset of angina attacks. These results suggest that platelet activation within the coronary circulation has some pathogenic role, probably as an aggravating factor, in coronary artery spasm.

Adult↗

Loss of nitric oxide production in the coronary circulation after the development of dilated cardiomyopathy: a specific defect in the neural regulation of coronary blood flow.

1. The aims of our study were to determine the role of nitric oxide (NO) in cholinergic reflex dilation of the coronary circulation in normal healthy conscious dogs and after the development of pacing-induced dilated cardiac myopathy and overt congestive heart failure. 2. Dogs were instrumented using sterile surgical techniques under general anaesthesia and allowed to fully recover. The Bezold-Jarisch reflex was stimulated by the intra-atrial injection of veratrine or the intravenous injection of PGI2, while the carotid chemoreflex was stimulated by the intracarotid injection of nicotine. Experiments were performed before and after the development of overt congestive heart failure (HF) caused by rapid left ventricular pacing for 4 weeks. 3. The release of NO, or NO-mediated vascular relaxation following administration of acetylcholine (ACh) may have little physiological significance since as ACh is released from nerve endings in vivo. Stimulation of the Bezold-Jarisch or carotid chemoreflex resulted in typical vagal cholinergic reflex coronary vasodilation, an increase in coronary blood flow and a decrease in coronary vascular resistance, which was substantially reduced following NO synthesis inhibition with nitro-L-arginine. 4. After the development of severe congestive HF, the production of NO by sieved coronary microvessels from the heart was markedly reduced accompanied by a 60-80% reduction in both the mRNA (northern blot) and protein (western blot) for endothelial NO synthase in the aorta. 5. After the development of severe pacing-induced HF, activation of the Bezold-Jarisch or carotid chemoreflex no longer resulted in coronary vasodilation due to the disappearance of NO production from the coronary circulation. 6. Therefore, cholinergic reflex coronary vasodilation is mediated by NO. Because coronary blood vessels lose the ability to produce NO after the development of HF, reflex cholinergic coronary vasodilation is markedly altered, uncovering a previously undiscovered specific defect in the integrated control of the coronary circulation in the failing heart.

Animals↗

Model of the coronary circulation based on pressure dependence of coronary resistance and compliance.

The effect of pressure-dependent changes in vascular volume, resistance and capacitance in the coronary micro-circulation, has been studied by a distributed mathematical model of the coronary micro-vasculature in the left ventricular wall. The model does not include regulation of coronary blood flow and is evaluated only for the fully dilated coronary vasculature. The left ventricular wall was thought to consist of eight parallel layers, each of them with an arteriolar, capillary and venular compartment. The resistance of each vessel was thought to depend on the inverse of squared volume, according to Poiseuille's Law for tubes with constant length. Tissue pressure has been assumed to be equal to left ventricular cavity pressure at the endocardium and to decrease linearly to atmospheric level at the epicardium. The pressure-volume relation of the vessel compartments were assumed to be sigmoidal. There is a rest volume at transmural pressure zero and delta V/delta P decreases with increasing transmural pressure. Simulation of experimental protocols described by other authors yielded results which were similar to the experimental outcomes, illustrated by: (1) a parallel shift to the flow axis of the pressure-flow curves due to cardiac arrest (2) steady-state endo/epi ratio of flow as a function of heart rate. It is concluded that interpretation of transients in coronary flow and/or pressure by models containing fixed resistance and capacitance may seriously underestimate intramyocardial capacitative effects and characteristic time constants for pressure-induced resistance changes.

Blood Pressure↗

Effect of azithromycin therapy on coronary circulation in patients with coronary artery disease.

This study examined the effect of azithromycin therapy on the coronary microcirculation using measurement of coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography in 35 patients with coronary artery disease. CFVR increased significantly after azithromycin therapy (3.0 +/- 0.7 vs 3.5 +/- 0.7, p <0.001). The changes in CFVR were negatively correlated with changes in high-sensitivity C-reactive protein levels in patients receiving azithromycin.

Aged↗