Effects of cocaine on canines' coronary arteries

Nine canines were anesthetized with pentobarbital and studied by both selective and semiselective coronary artery angiography following intravenous bolus doses of 1,3,5,8, or 10 mg/kg of cocaine. Catheterization was accomplished with a 5 Fr catheter over a 0.035 inch guidewire under fluoroscopic control, and angiograms were obtained by injection of a diatrizoate solution. Digital subtraction angiography (DSA) was performed prior to cocaine administration and at minutes 0.5, 1, 1.5, 3, 5, and, in some cases, minutes 10 and 15 after cocaine administration. The 1 and 3 mg/kg doses of cocaine had no effect on the coronary arteries. The 5 mg/kg dose significantly dilated the coronary arteries. The 8 mg/kg dose produced significant dilation at 30 seconds after cocaine but nonsignificant dilation of the coronary arteries at all other times. The 10 mg/kg dose produced significant dilation at 30 seconds, nonsignificant dilation at 60 seconds followed by significant constriction at 90 seconds after cocaine, which led to immediate death in most animals. The coronary dilation and constriction produced by 10 mg/kg of cocaine could be prevented by either preadministration or postadministration of naloxone, but this did not prevent subsequent death.     

Effects of dietary L-arginine on the reactivity of canine coronary arteries

Experiments were designed to determine the effects of supplemental dietary L-arginine on the endothelial and smooth muscle function of canine coronary arteries. One group of dogs was fed the standard laboratory chow while another group was supplemented with 250 mg/kg per day L-arginine. All dogs had undergone bilateral reversed interposition saphenous vein grafting and received 325 mg/day oral aspirin. After 5 weeks of arginine feeding, left circumflex coronary arteries were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers. Concentration-response curves were obtained to L-arginine, UK-14,304 (alpha2-adrenergic agonist) and A23187 (calcium ionophore) in the absence and presence of N(G)-monomethyl-L-arginine (L-NMMA) and tetraethylammonium (TEA) alone or in combination. Serum concentrations of L-arginine increased by about 20% following 2 weeks of arginine feeding and remained elevated throughout the study. In rings with and without endothelium contracted with prostaglandin F2alpha, L-arginine caused concentration-dependent contractions in rings from control animals but no significant change in tension in rings from arginine-fed animals. Contractions to L-arginine in control animals were reduced by either L-NMMA or TEA. Endothelium-dependent relaxations to the alpha2-adrenergic agonist were decreased with arginine feeding while relaxations to the calcium ionophore and the endothelium-derived factor nitric oxide were similar among groups. Relaxations to UK-14,304 were reduced by L-NMMA in both groups but by TEA only in rings from control animals. These results suggest that dietary supplementation with L-arginine modifies reactivity of endothelium and smooth muscle by at least two mechanisms: one associated with activation of potassium channels and the other with receptor-coupled release of nitric oxide.     

Effects of dopamine on isolated canine coronary arteries.

Dopamine contracted isolated canine coronary arteries at initial concentrations of 5 times 10(-6) mol/l. In the presence of phentolamine or phenoxybenzamine and after contraction of the arteries with K+ or prostaglandin F2alpha, dopamine caused dose-related relaxation at initial concentrations of 5 times 10(-6) mol/l and 10(-6) mol/l. Propranolol, 10(-6) mol/l, and haloperidol, 10(-5) mol/l, did not antagonize the relaxation.     

Effects of tetrahydrobiopterin on coronary vascular reactivity in atherosclerotic human coronary arteries

OBJECTIVES: Reduced nitric oxide (NO) bioavailability is a key mechanism in the development of endothelial dysfunction. The NO synthase cofactor, tetrahydrobiopterin (BH4), increases NO availability, yet its effect in the human coronary circulation, particularly following PCI, remains uncertain. This study was designed to evaluate the effects of intracoronary BH4 in human coronary arteries with non-critical coronary artery disease or following percutaneous coronary intervention (PCI). METHODS: The study group consisted of 57 stable patients, 10 of which were controls. Active drug was administered in 47 patients, with either de novo non-critical coronary disease (non-stent group; n=25) or following PCI (stent group; n=22). Coronary blood flow (CBF) was measured (0.014-inch Doppler flow wire) in each of these groups in response to sequential intracoronary infusions of acetylcholine (Ach, 10(-7) & 10(-6) M), BH4 (250 mug/min & 500 mug/min) and a co-infusion of BH4 (500 mug/min) and Ach (10(-7) & 10(-6) M). The primary endpoint evaluated the % change in CBF to Ach compared to co-infusion of Ach and BH4. RESULTS: Mean age was 60+/-10 years (M 45:F 12). Regarding the primary hypothesis, no difference was observed between Ach response compared to co-infusion of BH4 and Ach in the % change in CBF in either the non-stent group (Ach 97+/-122%, Ach/BH4 87+/-95%) or the stent group (Ach 77+/-105%, Ach/BH4 55+/-97%). CONCLUSIONS: In native non-critical coronary artery disease or following PCI, coronary microvascular endothelial function is not improved by co-administration of Ach and BH4.     

降钙素基因相关肽对犬冠脉流量及冠状动脉的作用

本研究通过整体及离体灌流实验观察到重庆冠脉狭窄时，犬冠脉流量（ＣＢＦ），平均动脉压（ＭＡＰ）明显减小，而心率（ＨＲ）则增加。狭窄３０ｍｉｎ后由冠状动脉注射降钙素基因相关肽（ＣＧＲＰ）０．３μｇ／ｋｇ后，ＣＢＦ、ＭＡＰ和ＨＲ可恢复正常水平。同时，缺血犬的离体冠状动脉对ＣＧＲＰ的反应也出现改变。大冠脉舒张反应明显降低，而小冠脉的舒张反应与正常相比，无明显改变，这可能与缺血后大冠脉的内皮细胞容易损伤有关。同时也提示:急性心肌缺血时，冠脉流量的减少，主要由于小冠状动脉收缩所致。     

Effects of angiographic contrast medium on isolated canine coronary arteries

In isolated canine coronary arteries previously contracted by high potassium concentration, angiographic contrast medium decreased active tension by 61 +/- 2%. The relaxant effect was dose dependent and was not prevented by beta-blockade with d-l-propranolol (10(-5) M). This effect was similar to that obtained with nitroglycerin (10(-6) M), and further relaxation was evident when this vasodilator was administered after exposure to the contrast medium. When arteries were precontracted by alpha-receptor stimulation with norepinephrine (10(-5) M) at normal potassium concentration, a maximal relaxation of 83 +/- 6% was elicited after exposure to contrast medium. The relaxant effect could not be reproduced by a similar increase in osmolarity brought about by addition of sucrose. When arterial strips were processed by radioimmunoassay for dosage of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) after the relaxing action of the contrast medium occurred, a decrease in cAMP from 2.61 +/- 0.86 to 0.63 +/- 0.1 pmol/mg protein (p less than 0.05) was observed, whereas no significant changes in cGMP were detected. These nucleotides do not appear to be involved in the relaxant effect of the dye in the same way as they are when relaxation is elicited by some other coronary vasodilators.     

Safety of coronary ultrasound angioplasty: Effects of sonication on intact canine coronary arteries

The purpose of this work was to examine in vivo the safety of sonication in the coronary arteries in a live animal model. In intact dogs (n = 8), balloon dilatation was performed on the proximal left anterior descending artery (LAD) followed by sonication to the left circumflex artery (LCX) in power levels found to be optimal for thrombus ablation. Postdilatation and post-ultrasound coronary angiography, echocardiography, histopathology, CK-MB, indices of hemolysis, and coagulation were compared. Sonication did not induce changes in the ECG or blood pressure. Coronary angiography revealed no adverse side effects or change in arterial diameter (2.3 ± 0.7 vs. 2.4 ± 0.3 mm). Echocardiography showed transient opacification of the myocardium. Histopathology revealed a comparable minimal degree of endothelial denudation. After sonication there were no changes in the level of CK-MB (312 ± 168 vs. 283 ± 207 IU), hemoglobin (11.3 ± 0.9 vs. 12.7 ± 1.1 gr%), haptoglobin (479 ± 136 vs. 451 ± 121 mg/dL), fibrinogen (142 ± 18 vs. 165 ± 28 mg%), partial thromboplastin time (17.3 ± 3.2 vs. 17.6 ± 3.4 sec), prothrombin time (13.3 ± 7.8 vs. 11.5 ± 2.9 sec), and degree of platelet aggregation (55 ± 17 vs. 62 ± 8%). Thus, the data suggest that transluminal coronary sonication exerts no overt adverse effects in vivo. © 1995 Wiley-Liss, Inc.     

Effects of ketanserin on epicardial coronary arteries after coronary angioplasty in patients with stable angina

Previous studies have demonstrated the development of vasoconstrictionimmediately after percutanous coronary angioplasty (PTCA), distalto the dilated stenosis, presumably resulting from endothelialinjury. We have investigated the role of 5-HT₂ receptors inmediating vasomotor changes in proximal and distal coronarysegments and coronary stenoses, immediately after successfulPTCA in patients with chronic stable angina. We compared theeffects of the intracoronary infusion of 1 mg ketanserin (5-HT₂receptor antagonist) on proximal and distal coronary arterialsegments immediately after PTCA in both vessels subjected toPTCA and control vessels. Coronary diameters, before and afterangioplasty and after ketanserin administration, of proximaland distal segments and coronary stenoses were measured by computerizedquantitative coronary angiography (CAAS system) in 12 patients(10 male, two female; mean age 54 ±6 years) with stableangina subjected to PTCA. After coronary angioplasty, vasoconstrictionwas observed in the segment distal to the dilated stenosis butnot in the distal segments of control vessels ( – 0.12± 0.04 and – 0.02 ± 0.02 mm respectively,P<0.05). After ketanserin infusion significant dilatationwas found in the distal segments of both PTCA vessels and controlvessels, but the dilatation was greater in the PTCA vessels(P<0.05). No significant changes were found in the proximalsegments of either PTCA or control vessels, or at the PTCA site.In conclusion, the vasoconstriction distal to the site of PTCAis mediated, at least in part, via 5-HT₂ receptors.     

Aneurysms of the coronary arteries

Report on a mycotic and arteriosclerotic aneurysm of the right coronary artery in a 13-year-old girl and a 43-year-old man. With the help of the casuistics and the existing literature the author adopts a definite attitude to genesis, frequency, localisation and complication of the aneurysma.     

Shunts between the coronary and pulmonary arteries with normal origin of the coronary arteries

Seven patients with shunts between the coronary and the pulmonary arteries with normal origin of both coronary arteries are described. Symptoms, when present, may be related to critical diversion of local blood flow or to the size of the shunt relative to total coronary blood flow. Maximal exercise testing may aid in finding those patients in whom the shunt leads to myocardial ischemia and may be a convenient way to follow up asymptomatic patients. These small shunts are frequently difficult to detect by sensitive methods; selective coronary arteriography proved to be the most helpful diagnostic procedure. Indications for surgery are not well established, but would include (1) relief of symptoms, (2) prophylaxis against complications of coronary artery disease and (3) the prevention of bacterial endarteritis.     

外源性睾酮对高脂饮食去势雄兔冠状小动脉的影响

目的 了解外源性睾酮对高脂饮食去势雄免冠状小动脉的影响。方法 雄性新西兰白兔35只随机分成对照组、单纯去势组、低睾酮血症补充组、生理睾酮血症补充组和高睾酮血症补充组共5组，除对照组外其余各组行去势手术，术后对后3组肌注十一酸睾酮（TU），剂量分别是3，6，12mg／kg，形成低睾酮血症、生理水平睾酮血症、高睾酮血症，测定血清雌二醇（E2）、睾酮（T）水平和E2／T比值的变化，动物于第12周末处死．心肌切片染色，测定肌间小动脉硬化发生率、内膜增厚发生率、计算内膜面积占有率（RIA）、内膜／中膜比值。结果 肌间小动脉粥样硬化发生率、肌间小动脉内膜增厚率、RIA、内膜／中膜：对照组与生理睾酮血症补充组相当且均明显低于单纯去势组、低睾酮血症补充组和高睾酮血症补充组（P〈0．05）。结论 补充生理水平的外源性睾酮能降低高脂饮食去势雄兔的冠状小动脉粥样硬化发生率、肌间小动脉内膜增厚率、RIA，改善内膜／中膜比值，从而改善动脉粥样硬化。     

外源性睾酮对高脂饮食去势雄免冠状小动脉的影响

目的 了解外源性睾酮对高脂饮食去势雄兔冠状小动脉的影响.方法 雄性新西兰白兔35只随机分成对照组、单纯去势组、低睾酮血症补充组、生理睾酮血症补充组和高睾酮血症补充组共5组,除对照组外其余各组行去势手术,术后对后3组肌注十一酸睾酮(TU),剂量分别是3,6,12 mg/kg,形成低睾酮血症、生理水平睾酮血症、高睾酮血症,测定血清雌二醇(E2)、睾酮(T)水平和E2/T比值的变化,动物于第12周末处死,心肌切片染色,测定肌间小动脉硬化发生率、内膜增厚发生率、计算内膜面积占有率(RIA)、内膜/中膜比值.结果 肌间小动脉粥样硬化发生率、肌间小动脉内膜增厚率、RIA、内膜/中膜:对照组与生理睾酮血症补充组相当且均明显低于单纯去势组、低睾酮血症补充组和高睾酮血症补充组(P＜0.05).结论 补充生理水平的外源性睾酮能降低高脂饮食去势雄兔的冠状小动脉粥样硬化发生率、肌间小动脉内膜增厚率、RIA,改善内膜/中膜比值,从而改善动脉粥样硬化.     

Effects of N-acetylcysteine on nitroglycerin-induced relaxation and protein phosphorylation of porcine coronary arteries

We investigated the effects of the sulfhydryl-donor, N-acetylcysteine (NAC), on nitroglycerin (NTG)-induced relaxation of the vascular smooth muscle. Addition of histamine to isolated porcine coronary arteries induced an initial rapid contraction followed by a gradual decrease in tonic contraction. NTG applied to the coronary artery strips before histamine caused relaxation of the histamine-induced rapid (3 min) and tonic (48 min) contraction. The inhibition of the tonic contraction by NTG was less at 48 min than at 3 min. Application of NAC (NTG-NAC) enhanced the relaxing effects of NTG on the histamine-induced tonic contraction rather than the acute contraction. In phosphorylation studies, changes in the phosphorylation of an intermediate filament, desmin, were parallel with changes in contraction in NTG-treated and NTG-NAC samples at 48 min. These phosphorylation changes of desmin at 48 min, which might be responsible for tonic phase contraction, were more extensive than those of myosin light chain (MLC) phosphorylation at 3 min, which might be responsible for acute contraction. These results suggest that treatment with the sulfhydryl donor, NAC, inhibited the phosphorylation of desmin associated with the enhancement of NTG-induced relaxation, which might be related to the mechanisms of recovery from NTG tolerance by sulfhydryl groups.