Biomedical subjects

H Tomoike

Publications and source records attributed to H Tomoike.

At least 181 records · Page 10Linked to original sources

PubMed1988

Ca-activated K channel in cultured smooth muscle cells of rat aortic media.

Electrical and pharmacological properties of the single Ca-activated K channel in cultured smooth muscle cells (SMC) of the rat aorta were studied with the patch-clamp technique. The Ca-activated K channel had a slope conductance (gamma K) of 135 +/- 2 pS (mean +/- SE; n = 5) in symmetrical 142 mM K solutions. The reversal potentials show a 56-mV change for a 10-fold change in the external K concentration. Probability of the channel opening increased when the intracellular Ca concentration ([Ca]i) was increased over 10(-7) M or the membrane was depolarized. The channel was blocked by either external tetraethylammonium (TEA, 10-30 mM) or by internal Ba (1-5 mM). Channel activities were characterized by burst-like openings. Open-time histogram was fitted with a single exponential (tau = 1.3 ms at +10 mV and 10(-7) M [Ca]i), whereas the closed-time histogram was fitted with two exponentials (tau 1 = 0.7 ms and tau 2 = 111 ms). The permeability ratio for monovalent cations calculated with the Goldman-Hodgkin-Katz equation was K:Rb:Na = 1:0.7: less than 0.01. We conclude from these observations that the Ca-activated K channel in cultured SMC of the rat aorta is characterized by a middle size gamma K, activation by [Ca]i increase and depolarization, relatively low sensitivity to TEA, and high selectivity for K ions.

Animals↗

PubMed1988

Effects of alpha-human atrial natriuretic peptide on the interrelationship of arterial pressure, aortic nerve activity, and aortic diameter.

A previous study has suggested that atrial natriuretic peptide (ANP) alters arterial baroreflex control of lumbar and renal sympathetic nerve activity. To explore these mechanisms, we examined the interrelationship of arterial pressure, afferent aortic nerve activity, and aortic diameter in rabbits anesthetized with alpha-chloralose before and after sinoaortic denervation and bilateral vagotomy. Arterial pressure was decreased in stepwise fashion by intravenous infusion of alpha-human ANP (alpha-hANP, 0.1-1.0 microgram/kg/min) or sodium nitroprusside (SNP, 1-5 micrograms/kg/min). Both in rabbits with intact baroreceptors and in those with baroreceptors denervated, aortic nerve activity and the aortic diameter decreased during hypotension caused by the infusion of SNP but remained unchanged during hypotension caused by the infusion of alpha-hANP. In addition, we examined the effects of alpha-hANP and SNP on the responses of the aortic diameter and aortic nerve activity to rapid changes in arterial pressure caused by intravenous phenylephrine or nitroglycerin. Changes in aortic nerve activity and the aortic diameter in response to rapid changes in arterial pressure caused by phenylephrine or nitroglycerin were not different between the infusion of alpha-hANP and SNP. These results suggest that aortic nerve activity remains unchanged despite hypotension during the infusion of alpha-hANP, because alpha-hANP dilates the aorta. Since the aortic diameter increases, strain of aortic baroreceptors does not decrease. A second suggestion is that alpha-hANP does not alter aortic baroreceptor responses to changes in arterial pressure caused by phenylephrine or nitroglycerin.

Animals↗

PubMed1987

Collateral function modified by glyceryl trinitrate and dipyridamole during coronary occlusion in conscious dogs.

The effects of glyceryl trinitrate and dipyridamole on induced ischaemia were studied in awake dogs during transient coronary occlusion before and after collateral development. Seventeen dogs were instrumented under sterile conditions with a miniature pressure gauge to measure left ventricular pressure, a cannula for aortic pressure, and pairs of piezoelectric crystals towards the subendocardium of the left ventricle for regional segment length measurements. A hydraulic cuff occluder and Doppler flow probe were placed around the left circumflex coronary artery. Collateral function was increased by repeated 2 min coronary occlusions at 32 min intervals for 2-9 days until regional wall motion returned to preocclusive values, despite the persistence of coronary occlusion. The effects of glyceryl trinitrate and dipyridamole were studied after the initial haemodynamic changes had subsided. Collateral function was quantified by integrating changes in end systolic length of the ischaemic area during coronary occlusion. Before collateral development the end systolic length area was 29.4(2.4) cm X s and was unchanged by glyceryl trinitrate or dipyridamole. After the development of collaterals the end systolic length area decreased from 4.1(1.1) to 2.2(1.0) cm X s (p less than 0.01) after glyceryl trinitrate and increased to 14.9(1.7) cm X s (p less than 0.01) after dipyridamole. Therefore, glyceryl trinitrate acted directly on collaterals and improved the induced ischaemia, whereas dipyridamole exaggerated the regional wall motion abnormality.

Animals↗

PubMed1987

Leukotriene C4- and D4-induced diffuse peripheral constriction of swine coronary artery accompanied by ST elevation on the electrocardiogram: angiographic analysis.

Effects of leukotriene (LT) C4 and LTD4 on coronary artery spasm in atherosclerotic miniature pigs were examined angiographically. Endothelial balloon denudation of the left circumflex coronary artery was performed in 15 Göttingen miniature pigs; 11 were fed a 2% cholesterol diet and four were fed a regular diet for 3 months. Three months after this denudation, the area of the coronary artery was reduced by 94 +/- 2% and 43 +/- 5% (p less than .01) in the denuded and nondenuded areas by the intracoronary administration of 10 micrograms/kg histamine after pretreatment with 60 mg/kg iv cimetidine. The effects of LTC4 and LTD4 on coronary diameter and the preventive effects of FPL-55712, a LTC4 and LTD4-receptor blocker, or diphenhydramine, a histamine H1-receptor blocker, on histamine-induced coronary spasm were then examined angiographically. Administration of LTC4 or LTD4 in doses of 1 and 10 micrograms into the left coronary artery, or selectively into the left circumflex and left anterior descending coronary arteries in a dose of 5 micrograms, led to the elevations in the ST segment on the electrocardiogram and there was delayed filling of the contrast medium in the peripheral coronary artery. However, these LTs provoked no augmented constrictions at any site on the epicardial coronary arteries (n = 15). Diphenhydramine, 1 mg/kg (n = 6), abolished the histamine-induced coronary spasm FPL-55712, 0.1 mg/kg, with which the LT-induced myocardial ischemia was abolished, did not prevent the histamine-induced coronary artery spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

PubMed1987

Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation.

Pathogenesis of coronary artery spasm induced by histamine in miniature pigs was studied angiographically in in vivo and in vitro conditions. Endothelial balloon denudation was performed and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. Regional hypercontraction of the coronary artery was documented by selective coronary arteriography, and the resulting myocardial ischemia was confirmed by ECG-ST changes. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of histamine-induced coronary constriction in the coronary spasm, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mm Hg. Histamine (10(-5) M) reduced the diameter of the coronary artery of the isolated heart by 29 +/- 4 and 67 +/- 3% (p less than 0.001) in nondenuded and denuded areas, respectively. These figures were similar to data obtained angiographically in vivo after the administration of histamine 10 micrograms/kg. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. The degree of focal constriction induced by histamine, defined as a percent of stenoses from the mean diameter of the areas of proximal and distal to the spastic site, was similar in in vivo (10 micrograms/kg i.c.) and in vitro (10(-5) M) conditions. KCl (40 mM) reduced both the denuded and nondenuded coronary artery diameter by 67 +/- 3% and 68 +/- 3% (NS), respectively. The dose-response relation of the coronary diameter to histamine was not influenced by pretreatment with the nerve transmitter blockers guanethidine (3 X 10(-6) M), atropine (10(-6) M), and tetrodotoxin (3 X 10(-7) M). Phenylephrine (10(-5) M) did not potentiate constriction of the denuded areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Attenuation of endothelium-related relaxation and enhanced responsiveness of vascular smooth muscle to histamine in spastic coronary arterial segments from miniature pigs.

Mechanism of coronary spasm was examined regarding endothelium-related relaxation and contraction produced by smooth muscle cells of spastic vessels isolated from Göttingen miniature pigs. In these pigs, coronary artery spasm was documented angiographically in vivo three months after endothelial denudation, and spastic and control segments of the coronary artery were suspended in organ chambers at their optimal length for generating tension. Applications of KCl (118 mM), acetylcholine(10(-9) to 10(-4) M), and PGF2 alpha (10(-8) to 3 X 10(-5) M) produced similar tension, at the respective doses, in both the spastic and control coronary arteries. During increasing concentrations of histamine (10(-8) to 3 X 10(-4) M; n = 14) and serotonin (10(-9) to 10(-5) M; n = 13), the maximum tension of the spastic vessel was 136 +/- 6 and 97 +/- 4%, respectively, of the tension produced by 118 mM KCl. That is significantly larger than seen in the control vessels: 98 +/- 4 and 74 +/- 4%, respectively. The ED50 to histamine and serotonin was also significantly less in the spastic vessels. After mechanical removal of the endothelium, the tension generated during the cumulative administration of histamine (n = 8) but not serotonin (n = 8) was larger in the spastic than the control vessels, thereby suggesting the presence of augmented responses of the smooth muscle to histamine in the spastic vessels. The increase in maximum tension after mechanical denudation was greater in the control than the spastic vessels in cases of histamine and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Prostanoids, coronary circulation and coronary artery spasm in open chest dogs and miniature pigs.

Effects of prostanoids on coronary circulation were studied in anesthetized open chest dogs with intact coronary arteries or in closed chest Göttingen miniature pigs with denuded vessels. In the latter model, coronary artery spasm was repeatedly provoked at the previously denuded area by histamine i.c. after pretreatment with cimetidine i.v., H2-blocker. In the canine model, prostacyclin (PGI2) dilated to a greater extent the diameter of the large epicardial coronary artery than did PGE2, and both equally reduced the total coronary resistance. Vasoconstrictive effects of carbocyclic thromboxane A2, a stable analogue of thromboxane A2 (TxA2) on the epicardial coronary artery was augmented from 1.1 +/- 0.3 to 6.5 +/- 1.3% (p less than 0.01) after pretreatment with cyclooxygenase inhibitors. In case of Göttingen miniature pigs 3 months after endothelial denudation and cholesterol freeding, neither PGI2 nor indomethacin prevented histamine-induced coronary artery spasm. Thiothromboxane A2, a stable analogue of TxA2, did not provoke coronary artery spasm in the animals. Therefore, prostanoids may not be crucial to the provocation or prevention of coronary artery spasm from which myocardial ischemia ensues.

Animals↗

PubMed1987

Quantitative analysis of regional wall motion in dogs in situ--characteristics of end-systolic pressure-length relation.

Regional wall motion was analyzed to deduce the muscle property unique to regional contractile states. End-systolic pressure length relations were evaluated under global changes in a contractile state, under selective intracoronary administration of inotropic agents to produce regional hypo- or hyper-kinesis, and before and after extension of size of the ischemia. Linearity of the end-systolic pressure-length relation was confirmed in each perturbation; however, the behavior of this relation with regard to changes in the slope and X-axis intercept differed among the three situations. When the contractile state was altered globally by intravenous administration of inotropic agents such as dobutamine and propranolol, the slope of the end-systolic pressure-length relation changed in a manner similar to that seen with the pressure-volume relation or stress-strain relation, with no significant changes in the X-axis intercept. Namely, the level of global cardiac function determined the slope of the end-systolic pressure length relation. When regional hypokinesis was produced pharmacologically by selective intracoronary infusion of lidocaine, the X-axis intercept moved rightward, depending on the degree of regional hypokinesis. Expansion in the size of the ischemic area also shifted the X-axis intercept rightward. The latter two phenomena suggested that the hypokinetic segments were stretched by the surrounding intact myocardium. Accordingly, end-systolic pressure-length relations provide useful information concerning the functional state of regional myocardium. The systolic properties of the regional myocardium rendered hypokinetic have to be quantified so as to include the total geometry of the heart.

Animals↗

PubMed1987

Effects of nicorandil on large epicardial coronary artery in conscious dogs.

The effect of 2-nicotinamidoethyl nitrate (nicorandil, SG-75, Sigmart) on coronary circulation was studied in conscious dogs, instrumented previously under sterile condition with sonomicrometers for the external coronary diameter measurement, and an electromagnetic flow plobe on the left circumflex coronary artery and a catheter into the thoracic aorta. Intravenous administration of nicorandil in doses of 10, 30, 100 and 300 micrograms/kg increased coronary blood flow dose-relatedly by 13 +/- 2, 24 +/- 3, 144 +/- 18 and 309 +/- 36%, respectively. Nicorandil also increased the diameter of the large epicardial coronary artery by 38 +/- 6, 71 +/- 11, 150 +/- 24 and 173 +/- 26 microns in doses of 10, 30, 100 and 300 micrograms/kg, respectively. To eliminate flow-dependent dilation of the coronary artery, the external diameter of the large epicardial coronary artery was measured during fixing the amount of coronary blood flow constant by a cuff occluder after intravenous administration of nicorandil, however, the degree of coronary diameter increase was not attenuated. Thus, nicorandil dilates both large and small coronary arteries in conscious dogs, the former dilation being independent from changes in coronary blood flow.

Animals↗

PubMed1987

Prompt relief of vasospastic angina by calcium antagonists.

A 57-year-old man had recurrent episodes of angina pectoris at rest. An electrocardiogram (ECG) during attack revealed transient ST elevations in leads V1 to V5. His symptoms were not relieved by sublingual nitroglycerin (TNG), but subsided promptly following sublingual or intravenous calcium antagonists. However, there was no difference between the degree of ST elevation on ECG recorded during the treatment of angina with either TNG or with calcium antagonist. Recurrent angina and painless ST elevation on Holter ECG recordings were prevented by a large dose of diltiazem. Coronary arteriography revealed only mild stenosis at the proximal portion of the left anterior descending coronary artery. It is suggested that coronary artery spasm was the cause of angina in this case and that sublingual or intravenous calcium antagonist was more effective in the treatment of acute attack of vasospastic angina than sublingual TNG.

Angina Pectoris, Variant↗

PubMed1987

Effects of verapamil and nitroglycerin on coronary and systemic hemodynamics in conscious dogs.

Effects of i.v. bolus administration of verapamil (10-300 micrograms/kg) and nitroglycerin (0.01-30 micrograms/kg) on coronary and systemic hemodynamics were studied in chronically instrumented conscious dogs. Verapamil in a dose of 10 micrograms/kg dilated the large epicardial coronary artery, increased the coronary blood flow and heart rate and decreased the aortic pressure. A reduction of left ventricular dP/dt was observed when over 30 micrograms/kg of verapamil was administered. Nitroglycerin in a dose of 0.01 micrograms/kg dilated the large epicardial coronary artery. Other variables such as coronary blood flow, aortic pressure and heart rate were influenced when over 0.1 micrograms/kg of nitroglycerin was given. The effects of these drugs on coronary and systemic hemodynamics were augmented when incremental doses were given. Duration of the increases in coronary diameter and coronary blood flow persisted longer after verapamil than after nitroglycerin. To estimate the changes in coronary diameter, independent of flow change, the effects of verapamil (100 micrograms/kg) and nitroglycerin (20 micrograms/kg) on the large epicardial coronary artery were reexamined when the coronary blood flow was maintained constant using a cuff occluder. The extent of coronary artery dilation, unaffected by coronary blood flow, was 62% with verapamil and 100% with nitroglycerin. Thus, although nitroglycerin preferentially and flow-independently dilates the large epicardial coronary artery, dilation of the large epicardial coronary artery after verapamil is augmented by the process of flow-induced arterial relaxation.

Animals↗

PubMed1986

Reactive dilation and late-hyperemic constriction of epicardial coronary artery after short coronary occlusion.

Coronary blood flow and epicardial coronary artery diameter were simultaneously measured by an electromagnetic or Doppler flow probe and a pair of ultrasonic crystals, respectively, during reactive hyperemia in conscious dogs. Reactive dilation appeared after the full appearance of reactive hyperemia and lasted for a period of 4-20 times the duration of the coronary occlusion. beta-Receptor blockade (propranolol, 1 mg/kg iv) attenuated both the reactive hyperemia in volume by 21-22% (P less than 0.01) and dilative responses of the epicardial coronary diameter by 27-28% (P less than 0.01), despite a nonsignificant attenuation of the resting or peak hyperemic coronary blood flow. When coronary blood flow was held constant during reperfusion, by an occluder distal to the ultrasonic crystals, the reactive dilation disappeared. A peculiar reactive constriction was noted when coronary occlusion was performed proximal to the site of the ultrasonic crystals. Appearance of this constriction was at 149 and 385 s after the release of 5 and 60 s of coronary occlusion, respectively. This late reactive constriction disappeared after pretreatment with alpha- (phentolamine, 1 mg/kg iv) and/or alpha- + beta-blockade, but not with beta-blockade alone, and it was not observed when the coronary diameter was measured proximal to the occluder. Thus reactive dilation of the epicardial coronary artery derives from an increase in coronary flow and is reduced by propranolol via a reduction in the hyperemic flow, suggesting a flow-dependent change in the diameter of the epicardial coronary artery. Reactive constriction is a local phenomenon following marked reduction in the coronary diameter and is abolished by alpha-adrenergic blockade with phentolamine.

Adrenergic alpha-Antagonists↗

PubMed1986

Histamine-induced coronary spasm in regions of intimal thickening in miniature pigs: roles of serum cholesterol and spontaneous or induced intimal thickening.

The pathogenesis of histamine-induced coronary spasm was examined angiographically and morphometrically in Göttingen miniature pigs. In five of 36 consecutive pigs that were 4 to 5 months of age, coronary spasm was provoked by the intracoronary administration of histamine, and the left coronary arteries were examined histologically without endothelial denudation (group 1). Endothelial balloon denudation of the major branch of the left coronary artery was performed in 31 of 36 pigs and five died during the procedure. The remaining 26 pigs were randomly allotted to one of two groups, one fed a cholesterol-supplemented (group 2, n = 13) and one fed a regular low-cholesterol diet (group 3, n = 13). After 3 months, serum cholesterol increased significantly from 57 +/- 6 to 222 +/- 27 mg/dl (p less than .01) in group 2, but remained unchanged (48 +/- 5 to 55 +/- 6 mg/dl) in group 3. Percent narrowing of the coronary diameter induced by 10 micrograms/kg ic histamine after administration of the H2 blocker cimetidine (60 mg/kg iv) was 39 +/- 3% and 24 +/- 2% (p less than .05 between groups 2 and 3) at the nondenuded site and 78 +/- 3% and 74 +/- 4% at the denuded site in groups 2 and 3, respectively (p less than .01 between nondenuded and denuded sites). Histamine-induced percent narrowing of the coronary diameter after cimetidine in group 1, 2, and 3 pigs correlated well with the degree of intimal thickness on an exponential curve (r = .92, p less than .001). Since percent narrowing at the intact site was 27% (n = 19) in all three groups, predicted histamine-induced percent narrowing at the spastic site, applying the geometric theory, was 33 +/- 3%. Accordingly, enhanced constriction of the coronary artery with intimal thickening in response to histamine can largely be explained by the acquired hyperresponsiveness of the vascular wall to autacoids. This phenomena, not related to the level of serum cholesterol, may be uniquely linked to the basic pathology of evolution of atherosclerosis.

Animals↗

PubMed1986

Transmural distribution of myocardial infarction: difference between the right and left ventricles in a canine model.

The evolution of myocardial infarction 24 hours after ligating both the right coronary artery and the obtuse marginal branch of the left circumflex coronary artery was examined in 33 anesthetized dogs. Postmortem coronary angiography and a tracer microsphere technique were used to determine risk areas and their collateral blood flows, respectively. The mean weight of the risk areas was 11.3 +/- 0.5 g (mean +/- SEM) in the right ventricle and 10.5 +/- 0.9 g in the left ventricle (NS). The weight of infarcted tissue was 5.7 +/- 0.7 g in the right ventricle and 5.2 +/- 0.9 g in the left ventricle (NS). In both ventricles, infarct weight was linearly related to risk area size, and the percent of risk area necrosis was inversely correlated with the extent of collateral flow at 24 hours of coronary ligation, defined as the mean myocardial blood flow inside the central risk area. Ratios of infarct to risk area between the subendocardial and subepicardial layers were 0.76 +/- 0.06 and 0.28 +/- 0.05 in the right and left ventricles, respectively (p less than 0.01, between ventricles, n = 31), which coincided well with subendocardial-to-subepicardial-flow ratios at 24 hours, ie, 0.86 +/- 0.04 in the right ventricle and 0.32 +/- 0.06 in the left ventricle (p less than 0.01). The regional distribution of myocardial infarction correlated well with flow distribution inside the risk area; the slope of these relations was similar between the subendocardium and subepicardium in the right ventricle, whereas in the left ventricle it was larger in the subendocardium than in the subepicardium. Thus, in the dog, the inherent change in the regional distribution of coronary collateral blood flow is an important modifier in the evolution of myocardial infarction, especially in the left ventricle.

Angiography↗

PubMed1986

Relations between collateral flow and tissue salvage in the risk area after acute coronary occlusion in dogs: a topographical analysis.

Localization of salvaged tissue after occlusion of the left anterior descending coronary artery due to collateral blood flow within the risk area was examined in a canine model using differential autoradiography. 125I tracer microspheres were injected into the left anterior descending artery preocclusively to define the perfusion territory as a risk area. 99mTc labelled human serum albumin microspheres were injected into both the left main and right coronary arteries 48 h after ligation to determine the collateral flow area. Using a cryotome, 50 micron transverse sections of the whole heart were taken, and 125I and 99mTc autoradiograms were obtained independently. The same specimens were stained by the nitroblue-tetrazolium method to demarcate the intact and infarcted myocardium. The tracings of the infarct, risk and collateral areas were compared and measured by a plainmeter. The collateral blood flow was distributed to 86, 55 and 42% of the epi, mid- and endo-cardial portions of the risk area respectively (P less than 0.001 between the epi- and mid- or endo-cardium). Within the collateral area 88, 58 and 63% of the epi-, mid- and endo-cardial portions were free of myocardial necrosis (P less than 0.001 between the epi- and mid- or endo-cardium). There was a close linear relationship between the size of salvaged and collateral areas (r = 0.96, P less than 0.001). Thus, a topographical analysis of the tissue salvage inside the risk area demonstrated the indispensable role of collateral blood flow for maintaining tissue viability.

Animals↗

PubMed1985

A peculiar extra heart sound after artificial pneumothorax in congenital pericardial defect: a diagnostic clue.

A 37-year-old man was admitted to the hospital in order to evaluate the cause of systolic ejection heart murmur and to treat his easy fatigability. The chest roentgenogram showed a marked protrusion of the left second and third arches of the cardiac silhouette. At the diagnostic procedure, 200 ml of air was injected into the left thoracic space. The chest roentgenogram revealed no sign of pneumopericardium, but an abnormal extra heart sound was audible. Addition of another 200 ml of air was needed to reveal a pneumopericardium on the chest roentgenogram. A peculiar extra heart sound after artificial pneumothorax may be useful for the early recognition of congenital pericardial defect.

Adult↗

PubMed1985

Coronary artery spasm induced in miniature swine: angiographic evidence and relation to coronary atherosclerosis.

In a swine model of coronary artery spasm, the pathogenetic role of coronary atherosclerosis was examined. Following endothelial balloon denudation of the left circumflex coronary artery (LCX), male miniature swine were fed a laboratory chow diet containing 2% cholesterol. Although there was no difference in the extent of coronary vasoconstrictive response to histamine, serotonin, and ergonovine between the left anterior descending coronary artery (LAD) and the LCX before the denudation, a constrictive response was significantly augmented along the denuded portion of the LCX 1 and 3 months after the denudation. Augmented vasoconstrictive responses to phenylephrine were never evidenced. Histamine was the most potent vasoactive agent, and coronary artery spasm was provoked repeatedly by intracoronary or intravenous administration of histamine in the presence or absence of cimetidine. The spasm was provoked only in the denuded portion of the LCX, the same area which was angiographically normal before the occurrence of the spasm. Histologically, atherosclerotic changes were predominant along the denuded portion of the LCX. Topologic correlation was suggested between the site of the spasm and the site of coronary atherosclerosis. It is concluded that in this swine model of coronary artery spasm, atherosclerotic changes may be an important causative factor, in terms of an activation of multiple receptor-operated calcium channels in the coronary artery.

Animals↗

PubMed1985

Histamine-induced spasm not significantly modulated by prostanoids in a swine model of coronary artery spasm.

The role of prostanoids in a swine model of coronary artery spasm was examined. Eighteen miniature pigs underwent endothelial denudation of the left coronary artery (left circumflex branch in 14 pigs and left anterior descending branch in 4 pigs) followed by high cholesterol feeding. Three months after the denudation, when coronary artery spasm was repeatedly provoked along the denuded portion of the coronary artery by histamine, the vasoconstrictive effect of thromboxane A2 and the preventive effects of indomethacin and prostacyclin against histamine-induced coronary artery spasm were examined. Intracoronary administration of thiothromboxane A2, 200 micrograms, a stable thromboxane A2 analog, failed to provoke coronary artery spasm (seven of seven cases) but nonselectively constricted the coronary artery by 33%. Intravenous administration of indomethacin, 2 mg/kg, or continuous intravenous infusion of prostacyclin, 50 ng/kg per min, failed to prevent histamine-induced coronary artery spasm (four of four and eight of eight cases, respectively), yet the spasm was all but prevented by intravenous pretreatment with diphenhydramine at a dose of 1 mg/kg. Thus, in this swine model, prostanoids may not play a primary role in the occurrence of coronary artery spasm.

Animals↗