Biomedical subjects

K C Dellsperger

Publications and source records attributed to K C Dellsperger.

At least 37 records · Page 2Linked to original sources

PubMed1996

Variability of regurgitation in Björk-Shiley mitral valves and relationship to disc occluder design: an in vitro two-dimensional color-Doppler flow mapping study.

BACKGROUND AND AIMS OF THE STUDY: Normal prosthetic valves have regurgitation that varies according to valve type and design. The Björk-Shiley prosthetic mitral valve is a tilting disc valve that has undergone design changes since its introduction. From 1969 to 1981, Delrin, was used to make the disc occluder. After 1971, the occluder was made from Pyrolite (i.e. Conical and Radiopaque-Spherical valves). Our aim was to quantify the regurgitation of Delrin and Radiopaque-Spherical Björk-Shiley prosthetic mitral valves with color-Doppler flow mapping in an in vitro model that simulates transesophageal echocardiography imaging. MATERIALS AND METHODS: Normal unimplanted Björk-Shiley Delrin (BSD), Björk-Shiley Radiopaque-Spherical (BSS) and explanted (17 +/- 3 yrs) BSD valves (25, 27, and 29 mm) were studied in a pulse duplication system. The regurgitant leakage volume of the valves was measured with an electromagnetic flow probe at flow rates of 3.0, 5.0, and 7.0 L/min, a pulse rate of 70 beats/min, and a mean systemic pressure of 100 mmHg. Color-Doppler flow mapping was performed with a 3.7 MHz transducer positioned on the atrial chamber at an image depth of eight centimeters. The maximal regurgitant jet areas were measured offline and averaged from three beats. RESULTS: Maximal jet area, measured with color-Doppler flow mapping, correlated with regurgitant leakage volume (r = 0.82). Normal unimplanted and explanted BSD valves had greater regurgitant leakage volumes and jet areas than BSS valves for all sizes and flow rates studied. Regurgitant jet areas of normal unimplanted and explanted BSD valves were similar. CONCLUSION: Knowledge of the type of Björk-Shiley valve is important in the clinical evaluation of regurgitation severity by transesophageal echocardiography. The echocardiographic appearance of regurgitation of BSD valves does not necessarily imply valve dysfunction.

Blood Flow Velocity↗

PubMed1996

Summary and recommendations.

It has been estimated that up to 7,000 patients with Björk-Shiley Delrin (BSD) heart valves may be alive as of January 1996, the range of implant durations being from 15 to 27 years. The clinical question was whether these BSD valves could be expected to continue to function satisfactorily or if prophylactic replacement might be warranted. The data presented in this supplement suggest that clinically important regurgitation due to wear of the Delrin disc may occur in some BSD valves years after implantation. Normally functioning valves, however, show more regurgitation than Björk-Shiley Radiopaque Spherical disc valves. Some regurgitation does not therefore necessarily indicate dysfunction of BSD valves. There were only two reported cases of inlet strut fracture. However, there are no reports of catastrophic failure associated with fracture of the Delrin disc. Engineering studies showed no reason to suspect an increased rate of failure of the Delrin disc due to fracture or fatigue. All of the data suggested that the BSD valve will continue to provide years of continuing service. Disc wear, if it occurred, was at a rate which allowed adequate time for diagnosis and non-emergency treatment. The data showed no reason to remove BSD valves prophylactically. Patients should be treated on an individual basis, according to the function of their own valve or valves.

Biocompatible Materials↗

PubMed1995

Impaired microvascular response to graded coronary occlusion in diabetic and hyperglycemic dogs.

The hypothesis that coronary microvascular responses to ischemia are impaired in diabetes was tested in 9 alloxan-treated (60 mg/kg i.v.), 8 hyperglycemic, and 16 control dogs. Arteriolar diameters were measured in intact beating left ventricle by use of stroboscopic epi-illumination and intravital microscopy with fluorescence microangiography. Coronary arterial diameters were measured during graded reductions in mean coronary perfusion pressure to 60 +/- 1 (SE) mmHg (mild stenosis), 39 +/- 1 mmHg (severe stenosis), and 26 +/- 1 mmHg (coronary artery occlusion). Blood glucose levels were 95 +/- 5, 264 +/- 17, and 277 +/- 15 mg/dl in control, diabetic, and hyperglycemic animals, respectively. In control dogs, arteriolar microvessels (< 100 microns) dilated (24 +/- 5, 31 +/- 5, and 26 +/- 6% change in diameter from baseline during mild stenosis, severe stenosis, and coronary occlusion, respectively). Diabetes or hyperglycemia prevented the normal dilatory response and resulted in decreases in microvascular diameter during decreases in perfusion pressure (-2 +/- 3, -4 +/- 3, and -15 +/- 4% change in diameter in diabetic animals and -11 +/- 2, -9 +/- 4, and -8 +/- 5% change in diameter in hyperglycemic animals). Large-vessel (> 100 microns) dilation was also significantly impaired in diabetic and hyperglycemic animals. Myocardial perfusion was significantly lower in the epicardium during a severe stenosis in diabetic and hyperglycemic than in control dogs. Because the ATP-sensitive K+ (KATP) channel mediates this response in normal animals, we tested the hypothesis that KATP channel responsiveness is impaired in diabetes and hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Thromboxane contributes to submaximal coronary dilation during myocardial ischemia.

OBJECTIVES: Thromboxane has been shown to contribute to coronary constriction in conduit coronary arteries during platelet aggregation at the site of a critical stenosis. Previous studies from our laboratory suggest that following a critical coronary stenosis, persistent vasomotor tone occurs. We tested the hypothesis that thromboxane is responsible for that increased tone. METHODS: To test this hypothesis, 14 mongrel dogs of either sex were anesthetized and subjected to a critical coronary stenosis where distal coronary perfusion pressure was reduced to 36 +/- 2 mm Hg. During the coronary stenosis, SQ 29,548 (thromboxane/endoperoxide receptor antagonist) was administered intravenously (0.2 mg/kg and 2.0 mg/kg). Coronary microvascular responses were observed by directly visualizing the epicardial microcirculation. Diameters were measured using intravital microscopy coupled to stroboscopic epi-illumination and jet ventilation to compensate for cardiac and respiratory-induced motion. RESULTS: Coronary microvessels were divided into small (< 150 microns) and large (> 150 microns) arterioles. During SQ 29,548 administration, small coronary arterioles demonstrated no additional dilation during a critical coronary stenosis. In contrast, coronary microvessels > 150 microns demonstrated a dose-dependent vasodilation to SQ 29,548 (0.2 mg/kg: 6 +/- 2%; 2.0 mg/kg: 11 +/- 4%; P < 0.05 vs. no change). A time control study in six additional animals demonstrated no significant microvascular diameter changes following a critical stenosis over the time course of SQ 29,548 administration. CONCLUSION: Endoperoxides contribute to poststenotic microvascular vasoconstriction in vessels 150-300 microns.

Animals↗

PubMed1994

Role of adenosine in vasodilation of epimyocardial coronary microvessels during reduction in perfusion pressure.

Previous studies in which an isolated heart or in situ constant pressure preparation was used suggested a minimal role for adenosine in autoregulatory control of coronary circulation. These results, however, are controversial, and the role of adenosine in autoregulation of flow in heart is uncertain. To test the hypothesis that adenosine mediates microvascular dilation in response to reduction in perfusion pressure (PP), we performed experiments in 41 open-chest chloralose-anesthetized dogs. Internal diameters (ID) of epicardial small arterioles < 100 mumol were measured with an intravital microscope and stroboscopic epiillumination synchronized to cardiac cycle. PP was reduced by graded stenoses of the left anterior descending coronary artery (LAD, mild stenosis PP = 60 mm Hg; critical stenosis PP = 40 mm Hg) and complete occlusion. 8-Phenyltheophylline (8-PT 10 microM) or adenosine deaminase (ADA 10 U/min) was topically superfused onto the heart. Arteriolar dilation induced by topically applied adenosine < or = 10 microM was completely blocked by 8-PT. Without 8-PT (vehicle group), mild critical stenosis and complete occlusion caused arteriolar dilation (percentage of change in diameter 8.6 +/- 2.6, 16.0 +/- 2.7, and 13.6 +/- 4.8%). 8-PT did not inhibit this dilation (8.5 +/- 2.8, 16.1 +/- 4.6, 15.1 +/- 5.7%, NS vs. vehicle group). Topically applied ADA significantly inhibited intravenously (i.v.) administered adenosine-induced arteriolar dilation. Without ADA, arteriolar dilation occurred (16.6 +/- 3.0, 28.2 +/- 4.3, 15.4 +/- 6.2%, at each PP). However, ADA did not inhibit dilation induced by gradual stenoses (10.6 +/- 1.4, 24.2 +/- 4.3, 17.5 +/- 6.9%, at each PP, NS vs. vehicle group).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1993

Transthoracic echocardiography for evaluation of hypertensive heart disease.

Systemic arterial hypertension is a common malady in the United States, with as many as 58 million persons having a diagnosis of hypertension. Left ventricular hypertrophy (LVH), which develops as a response to the elevated afterload, may be viewed as necessary and protective. However, many recent studies have demonstrated that significant abnormalities of the coronary circulation occur with LVH. These include impaired vasodilator reserve, altered autoregulation, increased tendency to ventricular arrhythmias, and increased infarct size. In addition, adverse effects directly on cardiac muscle which includes decreased contractility, and altered diastolic function may also be present. Therefore, the presence or absence of LVH may predict outcome in addition to hypertension alone. In this review I will discuss potential advantages and disadvantages of each transthoracic echocardiographic method of measuring LV mass. I will also discuss the controversy surrounding serial measurements of LV mass with antihypertensive therapies.

Antihypertensive Agents↗

PubMed1992

Effect of hypertension and hypertrophy on coronary microvascular pressure.

We tested the hypothesis that transmural differences in coronary microvascular pressures may be greater in the setting of hypertension and left ventricular hypertrophy. Epicardial and endocardial microvascular pressures were measured in isolated lidocaine-arrested hearts during adenosine vasodilation. In both normotensive (n = 19) and hypertensive (one clip, one kidney, n = 10) dogs, microvascular pressures in endocardial arterioles at 60, 70, 80, 90, and 100 mm Hg of left main coronary perfusion pressures were lower than in epicardial arterioles (p less than 0.05 at all perfusion pressures). The pressures in epicardial arterioles as a percentage of the left main coronary perfusion pressure were similar in normotensive versus hypertensive hearts at all perfusion pressures. In contrast, the pressures in endocardium at 90 and 100 mm Hg of perfusion pressure were significantly (p less than 0.05) lower in dogs with hypertension and hypertrophy than in the controls (41 +/- 4 versus 50 +/- 2 and 40 +/- 4 versus 50 +/- 3 mm Hg at 90 and 100 mm Hg of perfusion pressure, respectively). Thus, there is a greater transmural resistance to microvascular perfusion in hearts with myocardial hypertrophy secondary to hypertension. This is likely due to differences in the vascular anatomy, secondary to hypertension and hypertrophy, and may contribute to vulnerabilities in subendocardial ischemia encountered in this condition.

Animals↗

PubMed1991

Hypertension and the coronary circulation. With special attention to endothelial regulation.

Calcium channel antagonists are commonly used to treat chronic hypertension. Several studies of intact vascular tissues suggest that these agents may impair the production of the endothelium-derived relaxing factor and alter endothelium-dependent vascular relaxation. These studies are difficult to interpret because the calcium channel antagonist may have direct effects on vascular smooth muscle. In our study, a chemiluminescence assay was used to measure the release of nitrogen oxides from bovine aortic endothelial cells (BAEC) grown in monolayer. Under basal conditions, the release of nitrogen oxides was 0.2 nmol/100 mg protein and was increased approximately two-fold by 0.1 micrograms, bradykinin. Incubations with diltiazem, verapamil, and nifedipine for 60 min did not influence the basal and bradykinin-stimulated release of nitrogen oxides by BAEC. These data illustrate that the production of the endothelium-derived relaxing factor is not altered by the calcium channel antagonist, and are compatible with an absence of L-type calcium channels in vascular endothelial cells. Chronic hypertension produces myriad adverse effects in the coronary circulation. After coronary occlusion, infarct size, expressed as a function of myocardial mass perfused, is increased by 33%, and the wavefront of infarction from subendocardium to subepicardium is hastened. Both chronic and acute hypertension produce numerous abnormalities of coronary flow regulation. These include impairments of autoregulation, changes in vascular responsiveness, and alterations of endothelial cell function. Many of these may worsen the clinical consequences of ischemic heart disease, either by producing structural alterations of the coronary vasculature, or equally importantly, by altering coronary vascular responsiveness to either mechanical or neurohumoral stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of coronary artery occlusion in animals with hypertension and left ventricular hypertrophy.

Chronic arterial hypertension (HT) and left ventricular hypertrophy (LVH) increase the morbidity and mortality of acute myocardial infarction in patients. In this article, we discuss earlier studies from Koyanagi et al. in our laboratory that showed that when animals with chronic HT and LVH (HT-LVH) were subjected to acute coronary artery occlusion (CAO), there was a 3.5-fold increase in mortality and a 35% increase in infarct size expressed as a percent of the area at risk. We subsequently determined the effect of HT-LVH on the wavefront of myocardial infarction. Dogs were made hypertensive using a single-kidney, single-clip model of renovascular hypertension that produced mean arterial blood pressure (BP) = 141 +/- 3 mm Hg and left ventricular:body weight = 5.8 +/- 0.1 g/kg (p less than 0.05 vs. control animals). Conscious animals with HT-LVH and control animals were subjected to 1 or 3 h of CAO. Infarct and risk areas were measured using triphenyltetrazolium chloride (TTC) stain and barium angiography, respectively. The results suggested that the wavefront of infarction was accelerated in animals with HT-LVH. Further studies suggested that the wavefront of myocardial infarction could be markedly retarded by normalizing blood pressure (nitroprusside) 1 h following CAO. Recent studies in an animal model of HT-LVH suggested that electrophysiological abnormalities occur when these animals were subjected to CAO. Sixty-five percent of animals with HT-LVH had sudden death during CAO compared to 27% of the control group. We studied whether chronic beta-adrenergic blockade would reduce mortality associated with CAO in animals with HT-LVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effect of an arginine analogue on acetylcholine-induced coronary microvascular dilatation in dogs.

The purpose of this study was to elucidate the contribution of endothelium-derived relaxing factor (EDRF) derived from arginine to acetylcholine (ACh)-induced coronary arteriolar vasodilatation in vivo. Experiments were performed in 62 open-chest anesthetized dogs. Internal diameters of small arterioles (less than 120 microns) and large arterioles (greater than 120 microns) were measured using an intravital microscope and stroboscopic epiillumination synchronized to the cardiac cycle. Topically administered NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-4) M) constricted small arterioles (-10.7 +/- 3.1% from control diameter, P less than 0.05), but L-NMMA did not produce vasoconstriction in large arterioles. ACh, in the absence of L-NMMA, caused a dose-dependent vasodilatation in both small and large arterioles. In large arterioles, L-NMMA completely abolished the ACh-induced vasodilatation (10(-5) M topical ACh: from 13.3 +/- 3.0 to -2.0 +/- 1.5%, P less than 0.05; 10(-4) M ACh: from 20.9 +/- 3.9 to -3.0 +/- 1.9%, P less than 0.01). In small arterioles, L-NMMA only partially inhibited the vasodilatation (10(-5) M ACh: from 35.4 +/- 4.0 to 19.0 +/- 2.7%, P less than 0.05; 10(-4) M ACh: from 42.5 +/- 4.8 to 22.6 +/- 3.1%, P less than 0.05). L-Arginine (10(-3) M topically) reversed L-NMMA inhibition of ACh-induced vasodilatation. Persistent dilatation of small arterioles also occurred when NG-nitro-L-arginine rather than L-NMMA was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1991

Coronary microvascular resistance in hypertensive cats.

Chronic systemic hypertension has been shown to alter the distribution of vascular resistance in many microvascular beds. The purposes of this study were to assess the effects of chronic systemic hypertension on the pressure distribution in the coronary microcirculation and to determine the microvascular site where coronary vascular resistance is increased. Cats were made hypertensive using a one-kidney, one-wrap model (Page model). A servonulling system was used to directly measure pressures in the epimyocardial microvessels of the beating left ventricle in normotensive and hypertensive cats. In chronically hypertensive cats, mean arterial pressure was 153 +/- 5 mm Hg compared with 98 +/- 3 mm Hg in normotensive cats (p less than 0.05). Left ventricular mass was increased approximately 34% in hypertensive cats (9.4 +/- 0.3 versus 7.0 +/- 0.3 g, p less than 0.05). Myocardial perfusion measured using radiolabeled microspheres was not different between hypertensive and normal cats. Coronary vascular resistance of the left ventricle was increased in hypertensive cats (0.90 +/- 0.08 versus 0.66 +/- 0.05 mm Hg x min x 100 g/ml, p less than 0.05). Microvascular pressures were measured in three groups of microvessels: small, less than 200 microns; medium, 200-300 microns; and large, greater than or equal to 300 microns. Mean microvascular pressures of large, medium, and small arterial microvessels in hypertensive cats were 144 +/- 8, 127 +/- 6, and 115 +/- 7 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Role of ATP-sensitive potassium channels in coronary microvascular autoregulatory responses.

The purpose of the present study was to test the hypothesis that ATP-sensitive potassium channels mediate autoregulatory vasodilatation of coronary arterioles in vivo. Experiments were performed in 23 open-chest anesthetized dogs. Coronary arterial microvascular diameters were directly measured with fluorescence microangiography using an intravital microscope and stroboscopic epi-illumination synchronized to the cardiac cycle. A mild coronary stenosis (perfusion pressure = 60 mm Hg), a critical coronary stenosis (perfusion pressure = 40 mm Hg), and complete coronary artery occlusion were produced with an occluder around the left anterior descending coronary artery in the presence or absence of glibenclamide (10(-5) M, topically), which inhibits ATP-sensitive potassium channels, or of vehicle. During topical application of vehicle (0.01% dimethyl sulfoxide), there was dilatation of small (less than 100 microns diameter) arterioles during reductions in perfusion pressure (percent change in diameter: 6.7 +/- 1.5%, 11.7 +/- 3.5%, and 10.4 +/- 5.1% during mild stenosis, critical stenosis, and complete occlusion, respectively). In the presence of glibenclamide, arteriolar dilatations during coronary stenoses and occlusions were abolished. Glibenclamide did not affect responses of arterioles greater than 100 microns. Glibenclamide did not alter microvascular responses to nitroprusside. These data suggest that ATP-sensitive potassium channels play an important role in determining the coronary microvascular response to reductions in perfusion pressure.

Adenosine Triphosphate↗

PubMed1991

Pathophysiology of myocardial perfusion in hypertension.

Chronic and acute hypertension have multiple untoward effects on the coronary circulation, several of which may either mimic or markedly worsen the clinical manifestations of coronary artery disease. Early after the onset of left ventricular hypertrophy secondary to hypertension, coronary vasodilator reserve is significantly impaired. During cardiac hypertrophy secondary to hypertension, the coronary arteries fail to enlarge in concert with ventricular enlargement. This failure results in a relative decrease by approximately 50% in the ratio of epicardial vessel diameter to the mass of myocardium perfused. The lower range of coronary subendocardial autoregulation is altered by chronic renovascular hypertension. A variety of vascular smooth muscle homeostatic mechanisms are abnormal in genetic models of hypertension, as is endothelium-dependent vascular relaxation. Acute hypertension may enhance constriction to serotonin, most likely through the release of potent vasoconstrictor substances from leukocytes and platelets that adhere to the endothelium as a result of endothelial damage. Finally, many of the consequences of myocardial infarction are worsened in the setting of hypertension and left ventricular hypertrophy.

Cardiomegaly↗

PubMed1990

Effects of left ventricular hypertrophy on the coronary circulation.

Many laboratories have provided evidence to support the concept that LV hypertrophy is associated with many significant coronary perfusion abnormalities. The decreased coronary flow reserve in the presence of LV hypertrophy is implicated as the mechanism of angina in patients with aortic stenosis and normal coronary arteries. The abnormal subendocardial autoregulation found in dogs may have important implications for the abrupt treatment of hypertension in patients with LV hypertrophy. The marked increase in mortality and the wavefront of infarction in dogs with hypertension and LV hypertrophy may have striking clinical implications for the salvage of myocardium in patients with chronic hypertension and LV hypertrophy during acute myocardial infarction.

Animals↗

PubMed1990

Effects of atherosclerosis on the coronary microcirculation.

We tested the hypothesis that atherosclerosis potentiates coronary vasoconstriction to serotonin and ergonovine. Coronary microvascular pressures and diameters were measured in the beating left ventricle in normal and atherosclerotic cynomolgus monkeys. Pressures were measured in arteries (190-350 microns diam) that were distal to atherosclerotic lesions. Microvascular pressure and simultaneous measurements of aortic pressure and myocardial blood flow were used to calculate segmental vascular resistance (large artery resistance and microvascular resistance) during serotonin, phenylephrine, and ergonovine dosages. Aortic pressure was maintained constant during all interventions. Administration of phenylephrine (50 micrograms.kg-1.min-1 iv) produced a similar increase in microvascular resistance from base line (P less than 0.05) in atherosclerotic and normal animals, 26 +/- 5 and 14 +/- 9 mmHg.min.g.ml-1, respectively. Serotonin (50 micrograms/min) did not influence coronary resistance in normal animals but produced a significant increase in both large artery (8 +/- 3 mmHg.min.g.ml-1) and microvascular resistance (21 +/- 6 mmHg.min.g.ml-1) in atherosclerotic animals (P less than 0.05). A higher dose of serotonin (200 micrograms/min) produced a modest increase in large artery resistance from base line in normal animals (3 +/- 1 mmHg.min.g.ml-1) and a greater increase in atherosclerotic animals (9 +/- 4 mmHg.min.g.ml-1) (P less than 0.05 vs. normals). Ergonovine (10 micrograms.kg-1.min-1 iv) elevated microvascular resistance in both normal and atherosclerotic animals (P less than 0.05) but increased large artery resistance only in atherosclerotic animals (10 +/- 4 mmHg.min.g.ml-1) (P less than 0.05). In summary, coronary vasoconstrictor responses to serotonin and ergonovine were potentiated by atherosclerosis. Because augmented constrictor responses to serotonin were observed in both the diseased arteries and the microcirculation of atherosclerotic animals, we speculate that the pathophysiological consequences of atherosclerosis extend into the microcirculation.

Adenosine↗

PubMed1990

Effects of acute coronary artery occlusion on the coronary microcirculation.

The exact microvascular site of coronary vasodilation after coronary artery occlusion has not been clearly established. We sought to determine 1) the microvascular site of recruitable vasodilator reserve after a critical stenosis as assessed by adenosine and EDTA, 2) the coronary microvascular site responsible for vasodilatation after total coronary artery occlusion, and 3) the microvascular site for recruitable vasodilator reserve after coronary artery occlusion as assessed by adenosine and EDTA. Hemodynamics and coronary epicardial microvascular diameter were measured in 33 dogs by means of intravital epiillumination microscopy at control conditions, during a critical stenosis, or 30, 60, and 120 min following coronary artery occlusion. To evaluate the site of pharmacologically recruitable vasodilator reserve, EDTA or adenosine was suffused onto the epicardial surface. After a critical stenosis EDTA dilated all sizes of microvessels, whereas adenosine only dilated small microvessels (less than 150 microns). After coronary artery occlusion there was vasodilation that was inversely proportional to the control microvascular diameter. Coronary microvascular diameter did not change during 2 h after coronary artery occlusion. In addition, intravenous or topically applied adenosine or topically applied EDTA had no additional effect on the coronary arteriolar diameter. We concluded that in response to sudden coronary artery occlusion, the coronary microvascular dilation was inversely related to the control microvascular diameter, and in contrast to the response after a critical stenosis, there was no pharmacologically recruitable vasodilator reserve to adenosine or EDTA following acute coronary artery occlusion.

Acute Disease↗

PubMed1990

Understanding the coronary circulation through studies at the microvascular level.

Studies of the coronary circulation have divided vascular resistances into three large components: large vessels, small resistance vessels, and veins. Studies of the epicardial microcirculation in the beating heart using stroboscopic illumination have suggested that resistance is more precisely controlled in different segments of the circulation. Measurements of coronary pressure in different sized arteries and arterioles have indicated that under normal conditions, 45-50% of total coronary vascular resistance resides in vessels larger than 100 microns. This distribution of vascular resistance can be altered in a nonuniform manner by a variety of physiological (autoregulation, increases in myocardial oxygen consumption, sympathetic stimulation) and pharmacological stimuli (norepinephrine, papaverine, dipyridamole, serotonin, vasopressin, nitroglycerin, adenosine, and endothelin). Studies of exchange of macromolecules in the microcirculation using fluorescent-labeled dextrans have also identified the size of the small pore (35-50 A) in coronary microvessels that can be altered by myocardial ischemia. Studies of the coronary microcirculation have demonstrated that the control of vascular resistance is extremely complex, and mechanisms responsible for these heterogeneous responses need further examination.

Animals↗

PubMed1990

Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.

Because beta-adrenergic blockade has as one of its many effects altered electrophysiological abnormalities after dogs with left ventricular hypertrophy have been subjected to coronary occlusion, we tested the hypothesis that metoprolol (200-400 mg/day) would reduce mortality rates in dogs with one-kidney, one clip left ventricular hypertrophy while a similar reduction in arterial pressure with enalapril (20-40 mg/day) would not. Dogs with left ventricular hypertrophy were given metoprolol or enalapril for 5-7 days before a 3-hour coronary occlusion. Infarct size and risk area were measured with triphenyltetrazolium chloride stain and barium angiography, respectively. For control (n = 15), left ventricular hypertrophy (n = 17), left ventricular hypertrophy plus metoprolol (n = 12), and left ventricular hypertrophy plus enalapril (n = 15) groups, mean arterial pressure, ratio of infarct size to risk area, and dogs experiencing sudden death were 110 +/- 4, 142 +/- 4, 121 +/- 7, and 120 +/- 3 mm Hg; 44 +/- 5%, 65 +/- 5%, 44 +/- 7%, and 30 +/- 4%; and 27%, 65%, 17%, and 53%, respectively. Thus, the excessive increase in early mortality occurring when dogs with hypertension and left ventricular hypertrophy undergo coronary occlusion is interrupted with beta-blockade, possibly via electrophysiological effects rather than by changes in arterial pressure or infarct size.

Adrenergic beta-Antagonists↗