Dynamic analysis of the three-phasic vascular response to histamine in coronary circulation

In this work we tried to perform a dynamic analysis of coronary vascular response to histamine, using a simple mathematical analysis as a first step in the better understanding of complex histamine effects on coronary blood vessels of the isolated guinea pig heart. So, we defined more parameters, such as: I and delta I to quantify the intensity of coronary perfusion pressure (CPP) change, T and dt to quantify the time CPP change occurs and D to characterize the intensity and duration of CPP change, i.e. to quantify the dynamics of this change.     

Mechanism of action of nonachlazin on nervous regulation of coronary circulation

In experiments on cats and dogs under general anesthesia nonachlazine, a new antianginal agent, depressed the reflex decrease of the blood flow to the coronary arteries (electromagnetic recording). Nonachlazine also depressed the reflex decrease of the blood flow in the system of common carotic artery, and the pressure vasomotor reflexes. During recording the tonic and reflex activity in the heart sympathetic nerves nonachlazine proved to selectively inhibit the vasoconstrictor impulses from Adelta-afferent fibers of the spinal nerves, that is it influenced the vasomotor component of the "primary" pain reaction. This mechanism could underlie the block by nonachlazine of the pain syndrome during the heart ischemia disease.     

Role of nitric oxide in regulation of brain stem circulation during hypotension

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-5) mol/L and 10(-4) mol/L N(omega)-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.     

Assessing the coronary circulation in hypertension

Systemic arterial hypertension is one of the major risk factors for coronary artery disease, coronary microangiopathy, and left ventricular hypertrophy, all of which can potentially lead to cardiac failure and sudden cardiac death. Coronary flow reserve is defined as the maximal increase in coronary flow above its resting, autoregulated level for a given perfusion pressure. In arterial hypertension functional and structural alterations are observed at the level of epicardial vessels as well as in resistive vessels requiring sophisticated approaches to assess coronary flow reserve and thus myocardial perfusion. Electrocardiographic tests and echocardiography can be regarded as monitoring and screening methods. Myocardial scintography is useful to semiquantitatively estimate hypertension-associated perfusion abnormalities, whereas positron emission tomography provides the only quantitative approach of a non-invasive technique for myocardial blood flow measurement. Invasive methods for the assessment of coronary blood flow need cardiac catheterization procedures, such as techniques requiring catheterization of the coronary sinus, angiographic methods, and guidewire based methods. Thermodilution and venous oxymetry in the coronary sinus systematically underestimate coronary flow reserve and are thus considered as only semiquantitative approaches. In contrast, the gas chromatographic argon method allows a quantitative measurement of coronary blood flow at baseline and during maximum vasodilation; thus it is possible to distinguish between an altered autoregulated and maximal flow as the major cause of a reduced coronary flow reserve and to evaluate long-term therapeutic interventions in hypertensive hearts. Videodensitometric and angiographic methods should be restricted only to patients with coronary microangiopathy or with coronary single-vessel disease. Guidewire-based Doppler techniques are suitable to semiquantitatively assess coronary flow reserve with a considerable spatial and time resolution. Myocardial biopsies may gain insight into hypertension-associated structural alterations in small arterioles. Long-term treatment of hypertensive heart disease aims to normalize blood pressure, to reduce left ventricular hypertrophy and to achieve cardioreparation including reversal of the abnormal structure and function of coronary circulation. Based on the different methods for assessment of coronary circulation the therapeutic value of different classes of antihypertensive therapeutics will be evaluated in this overview.     

Exercise training-induced adaptations in the coronary circulation

This paper focuses on a subset of homosexual boys whose mixed gender experience moves beyond the conventional categories of masculinity and femininity, and who are often labeled as pathological due to a reluctance to recognize the reality of gender variance and cross-gendered identifications within the domain of mental health. Clinical examples are offered to highlight the need for a theory of gender that accounts for the interweaving of gender and psychic structure as they co-evolve and reflect the chaos inherent in human subjectivity.     

Role of EDRF in the regulation of shear rate in large coronary arteries in conscious dogs

To determine whether dilation of large coronary arteries normalizes shear during increased flow following brief occlusion, six dogs were instrumented to measure aortic and left ventricular pressures, left circumflex coronary artery external diameter, and coronary blood flow. The coronary artery was occluded for 15 or 30 s. Data were obtained before and after blockade of EDRF synthesis with nitro-L-arginine. Internal coronary artery diameter and wall shear were calculated on a moment-to-moment basis and the area under the flow curve was measured. Peak flow and shear rate were unaffected by NLA or by the occlusion duration. Flow curve area increased with the duration of occlusion. Internal and external diameters increased significantly for 15 s occlusions before NLA (by 4 +/- 1% in external diameter and by 11 +/- 4% in internal diameter) and for 30 s occlusions before NLA (by 5 +/- 1% in external diameter and by 14 +/- 5% in internal diameter) but not after NLA. Adenosine infusions of 0.05, 0.10, 0.50, and 1.0 mumol/kg/min were also used to dilate the coronary arteries. With each infusion, flow, shear and diameter were allowed to reach steady state. Steady state shear was reduced only slightly and did not approach the baseline state. We conclude that increased shear rate causes an increase in coronary artery diameter which is EDRF dependent. Increased coronary artery diameter during reactive hyperemia and adenosine infusions did not normalize wall shear.     

Role of oxygen extraction from coronary blood in the regulation of oxygen transport to the myocardium

Experiments on anesthetized dogs were made to examine oxygen extraction from coronary blood during increase and decrease in cardiac rhythm frequency under varying conditions of vasomotor regulation. With an initially high tone of the coronary vessels both increase and reduction of myocardial oxygen supply occurred at the expense of vasomotor reactions. Under these conditions the coronary blood flow velocity and systolic rhythm correlated well. At the same time the oxygen level in coronary blood did not experience noticeable changes. As the initial tone of the coronary vessels dropped, vasomotor reactions were attenuated and oxygen extraction from coronary blood underwent alterations which had occurred prior to depletion of the coronary expanding reserves. The data obtained suggest that reduction of the initial tone of the coronary vessels proceeds non-uniformly, leading to a decrease in vascular sensitivity to the tissue oxygen level.     

Pathophysiology of coronary collateral circulation in the human

The functional relevance of coronary collaterals in humans has yet to be fully explored. Several studies demonstrated a protective role of collaterals in patients with coronary artery disease. On the other hand, negative aspects of well-developed coronary collaterals have been reported, e.g. a higher rate of restenosis following coronary angioplasty, or a redistribution of blood via collaterals away from the myocardial area in need towards normally perfused areas (coronary steal). In the past, the coronary collateral circulation has been assessed only qualitatively, using visual angiographic or nuclear imaging methods. With the recent advent of intracoronary Doppler and pressure-transducers, quantitative assessment of functional parameters of the coronary circulation has become feasible. This article reviews ongoing research in the field of coronary collaterals in humans, concerning their exact determination, the positive and negative aspects of their structure as well as their functional aspects.     

Studies of the coronary circulation in Chagas' heart disease

Pathogenesis of chronic Chagas' heart disease may include various disturbances in the coronary circulation, that could be responsible for the myocardial lesions seen in human hearts and in experimental models of the disease. In this paper we critically reviewed the anatomical and functional abnormalities described in chronic chagasic patients, pertaining to the so-called vascular pathogenetic theory of Chagas' disease. The epicardial coronary arteries are usually free of significant obstructive disease in nonselected groups of chagasic patients examined at autopsy or by coronary angiography. However, chagasic patients who were studied after an episode of acute myocardial infarction, show the same patterns of atherosclerotic coronary artery disease seen in the general nonchagasic population. Studies of chagasic patients with angiographically normal coronary arteries, by several scintigraphy methods, revealed myocardial perfusion abnormalities which may be caused by the microcirculatory derangements described in animals experimentally infected with the T. cruzi. Since hypoperfusion has been detected in regions with normal or mildly impaired wall motion, it is likely that the microvascular disturbances precede and may be causative mechanism for the subsequent myocardial damage. We speculate that hibernating ventricular areas may occur in chagasic patients, on the basis of the evidence gathered from these studies. Recent investigations of chronic patients with Chagas' disease and chest pain showed attenuation of the vasomotor responses to physiological and pharmacological stimuli, in the epicardial coronary arteries.     

Preoperative evaluation of coronary circulation

To define a strategy for coronary circulation assessment is a difficult task as most of the studies have been carried out in vascular surgery, as some of them are controversial, and as no test has a 100% sensitivity and specificity. However patients with high perioperative risk of cardiac events have to be identified, in order to intensify medical treatment or to consider myocardial revascularisation. A first evaluation is based on history, physical examination and simple tests, such as rest electrocardiogram and thorax X-Ray. Additional tests are not required when surgery does not elicit a major activity of the cardiocirculatory system. Postoperative cardiac risk is low when none of the nine risk factors defined by Goldman and/or coronary insufficiency (residual angina elicited by minor physical activity, unstable angina, myocardial infarction) are present. The problem remains in patients with Goldman risk factors and/or at risk of coronary artery disease because of diabetes mellitus, heavy smoking, hypercholesterolaemia, arterial hypertension, undergoing major abdominal, thoracic or vascular surgery. Preoperative electrocardiographic Holter monitoring is still of value, especially in patients with known or supposed ischaemic heart disease and unable to make a physical effort. A poor exercise capacity and changes in electrocardiographic stress testing are factors of poor prognosis. The dobutamine stress echocardiography has a good sensitivity and specificity when an effort test cannot be performed. The value of dipyridamole-thallium 201 scintigraphy could be improved by a quantitative analysis of the number of affected segments and territories. Patients with angina or ischaemic episodes on continuous electrocardiogram, or with dobutamine echocardiography kinetic disturbances and with stress myocardic scintigraphy or stress exercise testing abnormalities could undergo a coronarography, in order to consider myocardic revascularization prior to surgery.     

Advances in the study of neurohumors regulation of cerebrovascular circulation

During two outbreaks of respiratory syncytial virus (RSV) infection, 68 children with acute respiratory illnesses were cultured for RSV using a Rhino-Probe (RP) nasal curette and either a nasopharyngeal (NP) swab or a nasal wash (NW). In the first outbreak isolations of RSV by the RP nasal curette and NP swab methods were compared. RSV was cultured from 25 of 42 (60%) subjects using the RP nasal curette and from 20 of 42 (48%) subjects using the NP swab. In the second outbreak the RP nasal curette and the NW collection techniques were compared. RSV was isolated from 15 of 26 (58%) children evaluated. RSV was cultured from 14 of 15 (93%) patients by RP and 13 of 15 (87%) when using NW. In the group of culture-positive subjects, the TESTPACK RSV rapid antigen test was positive in 10 of 15 (67%) using the RP and in 6 of 15 (40%) using the NW. Like the NP swab the RP nasal curette was simple, noninvasive and relatively inexpensive, yet it was as sensitive as the NW for detection of RSV.     

Soluble P-selectin is released into the coronary circulation after coronary spasm

BACKGROUND: The glycoprotein P-selectin is an adhesion molecule involved in the property change of leukocytes at the initiation of the inflammatory process. The purpose of the present study was to determine whether acute myocardial ischemia induced by coronary spasm causes an acute inflammatory response in the coronary circulation. METHODS AND RESULTS: We examined plasma soluble P-selectin levels in the coronary sinus and the aortic root simultaneously in 16 patients with coronary spastic angina before and after left coronary artery spasm induced by intracoronary injection of acetylcholine and in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Ten control patients with chest pain but normal coronary arteries and no coronary spasm also received intracoronary acetylcholine. Plasma soluble P-selectin levels were increased significantly in the coronary sinus (32.8 +/- 3.6 to 52.8 +/- 5.9 ng/mL, P < .001) and in the aortic root (34.6 +/- 3.7 to 41.9 +/- 4.4 ng/mL, P < .05) after the attacks in the coronary spastic angina group but remained unchanged in the stable exertional angina group after the attacks and in the control group after the administration of acetylcholine. Furthermore, the coronary sinus-arterial difference of soluble P-selectin increased significantly after the attacks in the coronary spastic angina group (-1.8 +/- 2.2 to 10.9 +/- 2.7 ng/mL, P < .001). CONCLUSIONS: Our data indicate that soluble P-selectin is released into the coronary circulation after coronary artery spasm. We conclude that coronary artery spasm may induce the leukocyte adhesion in the coronary circulation and may lead to myocardial damage.     

Anatomical types of coronary circulation and various lesions of the right coronary artery

The data on coronarography, conducted in clinic to 1249 patients in 1994-1996 yrs., and intraoperative data, obtained in the patients with a coronaris dextra (ACD) affection and its concurrent affection with a coronaris sinistra (ACS) operated on in clinic in 1974-1996 yrs., were analyzed. It was established that the frequency of severe affection of endothelium of ACD while the existence of the left coronary blood circulation (CBC) type 2.5 times as higher than that while the presence of its right or balanced kinds. The most frequent atherosclerosis occurrence in the proximal ACD portion creates the anatomical prerequisites for the broad application of surgical treatment methods of coronary insufficiency.     

Nitric oxide modulates vascular permeability in the rat coronary circulation

1. The objective of the present study was to assess whether inhibition of nitric oxide (NO) production could modulate vascular permeability in the coronary circulation in conscious rats. 2. Intravenous injection of NG-nitro-L-arginine methyl ester (L-NAME, 2 mg kg-1) resulted in a slowly developing hypertension and evoked twofold increases in vascular permeability in the left ventricle and right atrium as measured by the extravasation of Evans blue dye. Maintenance of mean arterial blood pressure at the level observed following L-NAME injection by infusion of noradrenaline (620-820 ng kg-1 min-1) did not induce significant protein extravasation in the coronary circulation. 3. L-NAME treatment markedly enhanced (up to 490%) protein extravasation both in the left ventricle and right atrium in response to platelet-activating factor (PAF, 1.9 nmol kg-1, i.v.) and endothelin-1 (1 nmol kg-1, i.v.). Noradrenaline infusion potentiated (up to 69%) endothelin-1-induced protein extravasation. The permeability effect of PAF was only slightly enhanced by noradrenaline. 4. The present findings indicate that inhibition of endogenous NO synthesis leads to an increase in protein extravasation and to potentiation of the permeability effects of PAF and endothelin-1 in the coronary circulation. These results also suggest that NO may be an important regulator of vascular permeability under physiological and pathological conditions.     

Complete occlusion of the left main coronary artery and the importance of coronary collateral circulation

Study of four patients who survived complete occlusion of the left main coronary artery forms the basis of conclusions concerning the functional significance of coronary collateral circulation. Each of these patients had prominent collateral circulation from the right coronary artery. Global left ventricular function was maintained to the extent that congestive heart failure did not occur; the biplane ejection fraction was normal in the two patients where measurement was possible. The peak rate of systolic wall thickening by roentgen videometry in anterior left ventricular segments was normal in one patient and mild to moderately depressed in another. Experience with the patients described herein indicates that coronary collateral flow can provide critically needed circulatory support for the patient with coronary artery disease.     

Effect of nitroglycerin on regulation of cerebral circulation

Investigations carried out with the use of radioisotopic, electromagnetic and resistographic methods showed that nitroglycerine increased the cerebral circulation diminishing the tone of the intracranial vessels. The drug also markedly depressed the central regulation of the cerebral circulation; it suppressed the reflex reaction of the intracranial vessels and prevented the development of experimental disturbances of the cerebral circulation of adrenergic origin.