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Biomedical subjects

G W He

Publications and source records attributed to G W He.

86 records · Page 5Linked to original sources

Predominant alpha 1-adrenoceptor-mediated contraction in the human internal mammary artery.

alpha-Adrenoceptor agonists and antagonists are widely used perioperatively for internal mammary artery (IMA)-coronary artery bypass operations. To determine subtypes of alpha-adrenoceptors in the human IMA, we studied responses of isolated human IMA segments to alpha-adrenoceptor agonists, antagonists, and electrical stimulation in organ baths. The IMA ring segments (3 mm long) were set up at a physiologic and comparable condition according to their own length-tension curves. alpha 1-Agonist methoxamine (MO) induced 2.65 +/- 0.70 g force and alpha 1, alpha 2-agonist norepinephrine (NE) induced 4.07 +/- 0.70 g force. The contractions induced by both MO and NE were totally abolished by alpha 1-antagonist prazosin (0.1 microM) but not alpha 2-antagonist yohimbine. alpha 2-Agonist UK14304 induced only 0.39 +/- 0.17 g force, which was significantly less than that induced by MO or NE (p < 0.001). Contractions induced by electrical field stimulation (2, 10, 20 Hz) were decreased by alpha 1-antagonist prazosin 1 microM (p < 0.01) but potentiated by alpha 2-antagonist yohimbine. These results strongly suggest that in the human IMA the postjunctional alpha-adrenoceptors are predominantly of the alpha 1-subtype and therefore the alpha-adrenoceptor agonist-induced contraction and the sympathetic nerve stimulation-induced contraction is mediated mainly by activation of the alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

Contractility of the human internal mammary artery at the distal section increases toward the end. Emphasis on not using the end of the internal mammary artery for grafting.

The distal section of the internal mammary artery (3 to 4 cm proximal to the bifurcation) is often used for coronary grafting. This part of the artery is more pharmacologically responsive to vasoconstrictor agents than is its midsection. The present study was designed to test the hypothesis that the reactivity of the distal section of the internal mammary artery is inversely correlated to the diameter of the artery. The distal section of the human internal mammary artery was collected from aorta-coronary bypass grafts and studied in organ baths at a length of 3 mm. At the optimal point of the length-tension curves determined by a computer-iterative fitting technique, the diameter at 100 mm Hg, the maximal contraction forces and effective concentration causing 50% of the maximal response to vasoconstrictor agents U46619, potassium chloride, alpha-adrenoceptor agonists norepinephrine, methoxamine, and phenylephrine were recorded or calculated. The maximal relaxation and 50% response to glyceryl trinitrate in phenylephrine-precontracted internal mammary artery segments were also calculated. The contraction force was standardized by the circumference (grams per millimeter). Regression analysis between contraction force and diameter revealed that the contraction force induced by U46619 and potassium chloride was inversely correlated to diameter (r2 = 0.2, p < 0.05 in U46619-induced contraction and r2 = 0.2, p < 0.01 in potassium chloride-induced contraction). The contraction force induced by norepinephrine also had a trend inversely correlated to diameter (r2 = 0.2, p = 0.07). Glyceryl trinitrate-induced relaxation was not correlated to diameter. This study demonstrated that the contractility of the distal section of the internal mammary artery is inversely correlated to the diameter; that is, the smaller the diameter, the greater the tendency for spasm to develop. This suggests that trimming off the distal end of the internal mammary artery as much as possible may be the best way to prevent graft spasm and that superior results of left internal mammary artery grafted to the left anterior descending artery or the use of a "free graft" may be related to the shorter length (distal end is trimmed off) and less contractility of the graft.

Coronary Artery Bypass↗

Inhibitory effects of glyceryl trinitrate on alpha-adrenoceptor mediated contraction in the human internal mammary artery.

1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta-adrenoceptor mediated relaxation and that alpha-adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha-adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA--coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40-90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/- 0.06 -log M) and 20-90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/- 0.16 -log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8-38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9-39.3% (P greater than 0.05). The alpha 1-adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Mitral valve replacement combined with coronary artery operation: determinants of early and late results.

Mitral valve replacement combined with coronary artery bypass grafting has been reported as being associated with a higher mortality than either mitral valve replacement or coronary artery bypass grafting alone. Cause of mitral valve disease and severity of mitral regurgitation have been reported as related to mortality. To study the correlation of the cause of mitral valve disease and severity of mitral regurgitation to hospital mortality and long-term survival, we analyzed the results of 135 patients undergoing mitral valve replacement and coronary artery bypass grafting between June 1974 and August 1989. The hospital mortality was 11.8% (16/135). Fifteen preoperative and operative variables were tested for correlation with hospital or late mortality using univariate tests and multivariate regression. Advanced age (greater than 60 years), New York Heart Association functional class, and wall motion score were independently associated with hospital mortality (p less than 0.05). The cause of mitral valve disease and severity of mitral regurgitation were not related to hospital mortality or long-term survival (p greater than 0.05). The follow-up rate was 96.6% for the hospital survivors (115/119). Mean follow-up was 52.6 +/- 4.1 months. There were 35 late deaths. Survival was 91.9%, 89.9%, 78%, and 49.9% at 1, 2, 5, and 10 postoperative years, respectively. Preoperative New York Heart Association functional class and use of catecholamines during the postoperative intensive care period were independently related to late survival (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Weak beta-adrenoceptor-mediated relaxation in the human internal mammary artery.

The function of beta-adrenoceptors in the human internal mammary artery was studied in vitro to predict the way in which the internal mammary artery graft would respond to beta-adrenergic agonists and antagonists given in the perioperative period. Ring segments of the distal internal mammary artery obtained from patients not receiving beta-blocker therapy were mounted in organ baths and isometric wall force was measured. For comparison, similar experiments were conducted on segments of canine coronary artery, a vessel known to have powerful beta-adrenoceptor function. All arteries were precontracted with potassium or the thromboxane mimetic agent, U46619, before isoproterenol cumulative concentration-relaxation curves were constructed. In the human internal mammary artery, the maximum relaxation induced by isoproterenol was only 14% of the potassium-induced contraction and 24% of the U46619-induced contraction. These responses were weak compared with 54% and 86% for beta-adrenoceptor relaxation measured in corresponding experiments in the canine coronary artery. In all experiments, propranolol antagonized the relaxation induced by isoproterenol. These studies suggested that the human internal mammary artery has only a small number of beta-adrenoceptors. We conclude that beta-adrenoceptors would contribute little to the reactivity of the human internal mammary artery graft to sympathomimetic drugs.

Animals↗

Reactivity of human isolated internal mammary artery to constrictor and dilator agents. Implications for treatment of internal mammary artery spasm.

Perioperative spasm of the internal mammary artery (IMA) may occur after coronary artery bypass surgery. To establish the most appropriate dilator agent, we tested the reactivity of ring segments of human IMA in organ baths to various constrictor and dilator agents. We found that the thromboxane mimetic U46619 was the most potent IMA constrictor agent, followed by norepinephrine, serotonin, phenylephrine, and potassium chloride (K+). In K+- or U46619-precontracted IMA, glyceryl trinitrate and papaverine caused full relaxation. In K+-precontracted arteries, nifedipine, verapamil, and diltiazem caused full relaxation, but nifedipine was 15-fold more potent than the other calcium antagonists. In contrast, pretreatment of vessels with glyceryl trinitrate failed to alter subsequent contraction to U46619 or K+ while nifedipine pretreatment abolished subsequent contraction to K+ and reduced sensitivity of the IMA to U46619. We conclude that perioperative IMA spasm could be treated with the rapid-onset, nonspecific, vasodilator glyceryl trinitrate, but for prophylaxis of IMA spasm, calcium antagonists or specific receptor antagonists should be tested in the clinical setting.

Dose-Response Relationship, Drug↗

Butter-enriched diets reduce arterial prostacyclin production in rats.

Rats were fed diets containing 10%, 30% or 50% energy as fat derived predominantly from butter or lard. The protein content of the diets was maintained at 20%. After three weeks on the diets, the rats were killed and the following parameters measured: prostacyclin production in vitro from abdominal aorta and mesenteric artery; platelet aggregation to ADP and thrombin; fatty acid composition of the phospholipids in plasma, thoracic aorta and liver; smooth muscle reactivity and release of endothelial derived relaxing factor (EDRF) from aortic endothelium stimulated by acetylcholine. There was no significant effect of increasing fat content of the diets (neither lard nor butter) on platelet aggregation. In contrast, prostacyclin production in both the mesenteric artery and the abdominal aorta fell in a concentration-dependent manner in the butter-supplemented rats. However, no effect on prostacyclin production was detected in arteries from the lard-supplemented animals. The effects of the diets on prostacyclin (PGI2) production correlated very well with the changes in plasma, aortic and liver phospholipid arachidonic acid (AA) and eicosapentaenoic acid (EPA) contents. AA decreased in a concentration-dependent manner in the rats fed the butter-enriched diets but did not change in those fed the lard-enriched diets, whereas EPA rose in a concentration-dependent manner in the butter-fed rats and was unchanged in the lard-fed animals. The clear-cut effects of the butter-enriched diets on aortic phospholipid fatty acid composition and aortic PGI2 production were accompanied by a significant reduction in smooth muscle relaxation to EDRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Reactivity of the canine isolated internal mammary artery, saphenous vein, and coronary artery to constrictor and dilator substances: relevance to coronary bypass graft surgery.

The internal mammary artery (IMA) and saphenous vein (SV) are used routinely in coronary artery (CA) bypass graft surgery. The IMA may develop spasm during surgery, and the SV often develops spasm during removal from the leg. We sought to determine the relative reactivity of the canine CA, IMA, and SV to potential vasoconstrictor substances and especially to determine which vasodilator agents were effective in these different blood vessels. All vessels were arranged as ring segments suspended at optimal stretch in organ baths. Glyceryl trinitrate (GTN) caused relaxation of the three vessels but was less sensitive, less potent (as determined by EC50 values), and had a reduced range of relaxation in the IMA. Papaverine was less sensitive in the IMA as compared with the CA and SV. Nifedipine, verapamil, and diltiazem were potent relaxing agents in all three vessels when precontracted by K+, but were less potent in vessels contracted by the thromboxane mimetic U46619 or phenylephrine, especially in the SV. These studies highlight the marked differences in the response of IMA and CA to constrictor and dilator agents and reinforce the notion that calcium antagonists of different chemical classes have widely differing activities in vascular tissue.

Animals↗

Complete atrioventricular canal associated with tetralogy of Fallot or double-outlet right ventricle and right ventricular outflow tract obstruction: a report of successful surgical treatment.

Six patients, 4 of whom had complete atrioventricular (AV) canal and tetralogy of Fallot (TOF) and 2 of whom had double-outlet right ventricle with subaortic ventricular septal defect (VSD) and right ventricular outflow tract obstruction, were treated. Two of the patients with complete AV canal and TOF had a shunt procedure only. The other 4 patients underwent complete repair. All 6 patients survived the operation. Complete repair was performed through the right atrium using the two-patch technique. The size and shape of the VSD patch is important. Residual VSD after repair was common. Two patients have undergone successful reoperation for this problem. Another patient has a small residual VSD.

Child↗

Pulmonic regurgitation and reconstruction of right ventricular outflow tract with patch. An experimental study.

Twenty-five dogs were divided into three experimental groups. In each animal of Group I (10 dogs), one pulmonary valve leaflet was resected and a monocusp-bearing bovine pericardial patch was sewn into the right ventricular outflow tract. The monocusp was retracted to the patch with plicating sutures, and when the sutures were removed the monocusp became functional. In each animal of Group II (10 dogs), an incision was made in the right ventricular outflow tract along the anterior pulmonary valvular commissure and a bovine pericardial patch of adjustable width (one half, one, or one and one half times the diameter of the pulmonary valve ring) was sewn into the incision. Group III (five dogs) was the control group. During each situation of altered pulmonary valve function, in each experimental animal, the pulmonary blood flow and intracardiac pressures were measured. Pulmonary regurgitation was expressed regurgitant fraction (retrograde flow divided by net forward flow). We reached the following conclusions: In all situations where pulmonary incompetence was created, the regurgitant fraction was related directly to the width of the patch and was usually not more than half of the net forward flow when the width of the patch was less than one and a half times the pulmonary valve ring diameter. Regurgitant fraction was about half of net forward flow when one leaflet had been excised. The index of pulmonary artery diastolic pressure minus right ventricular end-diastolic pressure was sensitive and bore an inverse relationship to the degree of pulmonary regurgitation. An accurately placed monocusp-bearing patch restored pulmonary valve competence after excision of a cusp. In treating patients, we are encouraged to preserve as much pulmonary valve function as possible.

Animals↗

Effects of hyperkalemia on neonatal endothelium and smooth muscle.

BACKGROUND: Contradictory results have been reported regarding the effect of hyperkalemic cardioplegic or organ preservation solutions on endothelial and smooth muscle cells. The present study was designed to determine the effects of potassium concentrations and exposure times to hyperkalemia on endothelium-derived relaxing factor (nitric oxide) biosynthesis and release, and smooth muscle function in neonatal vessels. METHODS: Aortic rings taken from neonatal rabbits were studied in organ baths at physiologic pressure. The effect of Krebs' solution containing 5, 25, 50, or 100 mmol/L potassium incubated for 45 minutes (group 1), St. Thomas' Hospital cardioplegic solution containing 16, 25, 50, or 100 mmol/L potassium for 45 minutes (group 2), and Krebs' solution containing 5 and 50 mmol/L potassium or St. Thomas' Hospital cardioplegic solution containing 16 and 50 mmol/L potassium for 135 minutes (group 3) or 270 minutes (groups 4 and 5) was examined. The rings were then washed and contracted with U46619 (30 nmol/L). The ability to release endothelium-derived relaxing factor (nitric oxide) in response to acetylcholine was tested. RESULTS: The maximal relaxation induced by acetylcholine did not decrease in any group. Evidence of slight alteration of smooth muscle contraction was seen only in the rings incubated in Krebs' solution with 50 mmol/L potassium for 270 minutes (group 4) with unchanged maximal contraction and sensitivity to potassium (group 5). CONCLUSIONS: We conclude that after exposure for a limited time (4 1/2 hours), hyperkalemia per se does not significantly alter the function of endothelium to release endothelium-derived relaxing factor (nitric oxide) in response to acetylcholine and only slightly alters the contraction speed of smooth muscle in the neonatal rabbit aorta.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗