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Biomedical subjects

G W He

Publications and source records attributed to G W He.

At least 55 records · Page 3Linked to original sources
PubMed1997

Rare complication of retrograde cardioplegia: inner wall perforation of the right atrium.

Retrograde cardioplegia has been widely applied with satisfactory results. This report presents a case in which the retrograde cannula was inserted into the coronary sinus by penetrating the inner wall of the right atrium rather than through the orifice of the coronary sinus. Surgeons should be cautious of this possibility, particularly in patients with a dilated right atrium in which the space between trabeculae is enlarged and the atrial tissue is friable. Under this situation, the tip of the cannula is easily caught in such a space and may penetrate the wall of the right atrium, which affects the delivery of cardioplegia.

Aged↗
PubMed1997

Morphometric study of the right gastroepiploic and inferior epigastric arteries.

BACKGROUND: Based on earlier observations that the thickness of the intima and structure of the media may have an impact on the long-term patency of arterial conduits and the lack of detailed histologic studies of the right gastroepiploic and inferior epigastric arteries, we subjected both vessels to morphometric analysis with emphasis on their suitability as conduits in myocardial revascularization. METHODS: The right gastroepiploic and inferior epigastric arteries were harvested from 28 unselected individuals (mean age, 73.2 years) at autopsy, and the luminal diameter and the width of the intima and media were measured. RESULTS: At all levels of measurement (origin, 10 cm, and 15 cm), the luminal diameter of the inferior epigastric artery was significantly smaller than that of the right gastroepiploic artery (p < 0.05). The right gastroepiploic artery demonstrated only mild intimal hyperplasia. In contrast, the inferior epigastric artery showed substantial intimal hyperplasia within the first 1-cm segment (mean, 134 +/- 131 microns versus 50 +/- 49 microns for the corresponding segment of the right gastroepiploic artery; p = 0.01). Intimal hyperplasia was only mild in the remainder of the inferior epigastric artery. In both vessels, the media was muscular with rare dispersed elastic fibers. The mean thickness of the media ranged from 380 +/- 116 microns proximally to 155 +/- 70 microns distally for the right gastroepiploic artery, and from 316 +/- 86 to 165 +/- 70 microns, respectively, for the inferior epigastric artery. CONCLUSIONS: In myocardial revascularization, use of the right gastroepiploic artery may generally be preferable to use of the inferior epigastric artery. This recommendation is based on the larger luminal diameter of the right gastroepiploic artery as compared with the inferior epigastric artery, the significantly greater intimal hyperplasia in the first segment of the inferior epigastric artery, and the limitation that the inferior epigastric artery can be used only as a free graft. The rate of development of intimal hyperplasia in the right gastroepiploic artery, if used as an in situ coronary artery bypass graft, may be slow, approximating that of the right gastroepiploic artery in its natural environment.

Aged↗
PubMed1997

Radial artery has higher receptor-mediated contractility but similar endothelial function compared with mammary artery.

BACKGROUND: The radial artery (RA) has been used as an alternative arterial graft for coronary artery bypass grafting, but this artery has been suggested to be spastic. Endothelin-1 (ET) and angiotensin II (AII) have been measured with increased plasma concentrations during cardiopulmonary bypass. However, whether RA is reactive to these two important receptor-mediated vasoconstrictors is unknown. Also unknown is the endothelial function of this arterial conduit. This study was designed to compare RA and the internal mammary artery regarding the contractile characteristics to ET-1 and AII and endothelial function. METHODS: Ring segments of the RA and internal mammary artery taken from patients undergoing coronary artery bypass grafting were studied in organ chambers at a physiologic pressure. The contractility was determined from the contraction induced by ET-1 and AII as contraction force and the force normalized by circumference (g/mm). The endothelium-dependent relaxation was induced by the calcium ionophore A23187, a nonreceptor agonist, and substance P, a receptor agonist for endothelium-derived relaxing factors. Nitroglycerin was used to study the endothelium-independent relaxation. RESULTS: Both ET-1 and AII induced a higher contraction force (9.0 +/- 0.9 g, n = 12, versus 4.5 +/- 0.4 g, n = 38, p < 0.0001 for ET and 6.5 +/- 1.9 g, n = 7, versus 1.7 +/- 0.3 g, n = 8, p = 0.015 for AII) and normalized force (0.95 +/- 0.1 g/mm versus 0.66 +/- 0.05 g/mm, p = 0.007 for ET-1 and 0.8 +/- 0.2 g/mm versus 0.2 +/- 0.05 g/mm, p < 0.01 for AII) in RA than in the internal mammary artery. There were no significant differences detected between these arteries with regard to either endothelium-dependent (to substance P and A23187) or endothelium-independent (to nitroglycerin) relaxation (p > 0.05). CONCLUSIONS: We conclude that the human RA has a higher receptor-mediated contractility (to ET-1 and AII) but similar endothelial function compared to the internal mammary artery. The study reveals the nature of the more spastic characteristics of the RA, supports the necessity of a more active pharmacologic intervention to relieve spasm in the RA, and suggests that the similar endothelium-derived relaxing factor-mediated endothelial function of the RA compared with the internal mammary artery may be the basis for a satisfactory long-term patency.

Angiotensin II↗
PubMed1997

Superiority of hyperpolarizing to depolarizing cardioplegia in protection of coronary endothelial function.

OBJECTIVE: Hyperpolarizing cardioplegia has recently been proposed for myocardial protection. To compare the protective effect of hyperpolarizing cardioplegia and depolarizing (hyperkalemic) cardioplegia on coronary endothelium, we studied porcine coronary arteries in the organ chamber. METHODS: Relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) was used as the index of endothelial function because (1) hyperkalemia without ischemia does not impair the nitric oxide-mediated function according to previous studies and (2) EDHF relaxes vessels by hyperpolarizing the membrane potential. Therefore depolarizing cardioplegia may inhibit this function, but hyperpolarizing cardioplegia may preserve it. EDHF-mediated relaxation was induced by bradykinin and the calcium ionophore A23187 with the presence of indomethacin (7 micromol/L; INN: indometacin), a cyclooxygenase inhibitor, and N(G)-nitro-L-arginine (300 micromol), a nitric oxide biosynthesis inhibitor in U46619 (30 nmol/L)-induced precontraction. The vessels were exposed to either hyperpolarizing cardioplegic solution (the potassium-channel opener aprikalim, 0.1 mmol/L) or depolarizing cardioplegic solution (high potassium concentration, 20 mmol/L for A23187 and 50 mmol/L for bradykinin experiments) for 1 hour with a constant supply of oxygen to exclude the effect of ischemia. RESULTS: EDHF-mediated relaxation was significantly impaired in either A23187 or bradykinin studies (80.1% +/- 7.5% vs 24.9% +/- 14.2%, p = 0.004, n = 8 in each group for A23187, and 71.4% +/- 4.7%, n = 13, vs 40.5% +/- 12.9%, n = 7, p = 0.01, for bradykinin). The effective concentration causing 50% of maximal relaxation was significantly increased in the A23187 experiments with the treatment of hyperkalemia. In contrast, in aprikalim-treated arteries, the EDHF-mediated relaxation induced by either A23187 or bradykinin was unchanged. CONCLUSIONS: We conclude that EDHF-mediated coronary endothelial function is maximally preserved by hyperpolarizing cardioplegia but impaired by depolarizing cardioplegia. These findings support the use of hyperpolarizing cardioplegia in cardiac operations.

Animals↗
PubMed1997

Depolarizing cardiac arrest and endothelium-derived hyperpolarizing factor-mediated hyperpolarization and relaxation in coronary arteries: the effect and mechanism.

OBJECTIVES: Depolarizing (hyperkalemic) solutions are widely used to preserve organs for transplantation and for cardiac operations. We previously observed that exposure to hyperkalemia reduced endothelium-dependent, noncyclooxygenase- and non-nitric oxide-mediated relaxation. This study was designed to examine the mechanism of this effect with regard to K channels and the associated membrane potential changes. METHODS: Porcine coronary artery rings were studied in organ chambers. After incubation of the tissue with 20 or 50 mmol/L doses of potassium for 1 hour, the endothelium-derived hyperpolarizing factor-mediated relaxation in the artery and the membrane hyperpolarization in a single coronary smooth muscle cell were studied. RESULTS: The endothelium-derived hyperpolarizing factor-mediated relaxation induced by substance P, which could be significantly inhibited by the Ca(2+)-activated K channel blocker tetraethylammonium but only to a lesser extent by the adenosine triphosphate-sensitive K channel blocker glibenclamide, was significantly reduced. Substance P-induced hyperpolarization of the membrane potential was also significantly reduced by the hyperkalemic incubation with a significantly elevated resting membrane potential. CONCLUSIONS: Depolarizing arrest reduces endothelium-derived hyperpolarizing factor-mediated membrane hyperpolarization and relaxation by affecting mainly the Ca(2+)-activated K channels and by depolarizing the membrane for a prolonged period. We suggest that this is one of the mechanisms for coronary dysfunction after exposure to depolarizing (hyperkalemic) cardioplegic and organ-preservation solutions and that, therefore, "perfect" protection of the heart or other organs should restore the endothelium-derived hyperpolarizing factor-related endothelial function.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Valve repair for aortic insufficiency: surgical classification and techniques.

OBJECTIVE: Valve repair for aortic insufficiency may provide an alternative to aortic valve replacement in selected patients. This repair could be an attempt at permanent correction or palliation to allow the aortic annulus to grow and avoid the use of anticoagulation. Based upon a five-year experience, we proposed a classification according to valvular anatomy which could be a guide to patient and procedure selection. METHODS: Between September 1989 and February 1995, 44 consecutive patients underwent aortic valvuloplasty for aortic incompetence at our institution. Patients' ages ranged from 19 months to 76 years with a mean of 33 years. The etiology of aortic incompetence was congenital in 30 patients, degenerative in 7 patients, rheumatic in 5 patients, and infective endocarditis in 2. Aortic valve lesions were classified into three different types: type I, aortic annular dilation (8 patients); type II, excessive aortic leaflet tissue (12 patients); and type III, restricted leaflet motion with or without deficient leaflet tissue (24 patients). Type I needed commissural plication in 7 patients; and aortic annuloplasty, which was simple in 6 patients, and pericardial-augmented in 2. Type II necessitated midleaflet excision in 11 patients and leaflet plication in 7. Type III required leaflet extension in 19 patients, leaflet replacement in 1 patient, aortic valve commissurotomy in 13 patients augmentation commissurorrhaphy in 2, leaflet shaving in 4, and repair of leaflet perforation in 2. RESULTS: Postoperative echocardiography revealed a significant decrease in the degree of aortic incompetence. Mean follow-up was 2.6 +/- 1.4 years. There was no mortality. Patients improved as is evident by NYHA functional class postoperatively. Eight of the first 13 patients (18%) needed reoperation. Three of these reoperations were bail-out procedures, and 3 patients (7%) who underwent the leaflet extension technique were reoperated upon 19 months to 3 years later. Presently, 23 patients are without anticoagulation, 11 take aspirin and 2 receive coumadin for combined mitral procedures. CONCLUSIONS: Aortic valve repair provides a low risk option with satisfactory intermediate-term results for the treatment of aortic insufficiency in appropriately selected patients. Patient and procedure selection may be based upon the echocardiographic anatomy of the aortic valve, and a comparative risk benefit appraisal with valve replacement.

Adolescent↗
PubMed1997

Inhibition of vasoconstriction by potassium channel opener aprikalim in human conduit arteries used as bypass grafts.

AIMS: Potassium channel openers (KCOs) are of potential therapeutic value. Little is known about the effect of these drugs on human conduit arteries used as coronary bypass grafts. The purpose of this study was to determine the effect of the KCO aprikalim (RP52891) on human arteries used as coronary bypass grafts with emphasis on the possible difference in the inhibitory effect on depolarizing agent-mediated rather than receptor-mediated contraction. METHODS: Human internal mammary artery segments (IMA, n = 88) taken from 28 patients were studied. Concentration-relaxation curves for aprikalim were established in IMA precontracted with three vasoconstrictors (K+, U46619, and phenylephrine). In IMA rings incubated with aprikalim (1 or 30 microM) for 10 min concentration-contraction curves for the three vasoconstrictors were constructed. RESULTS: Aprikalim-induced relaxation was less in K+ (37.3 +/- 6.4%) than in U46619 (80.2 +/- 7.7%, P=0.002), or phenylephrine (67.5 +/- 7.0%, P=0.038) -precontracted IMA. The EC50 for K+-(-5.40 +/- 0.12 log M) was significantly higher than that for phenylephrine (-6.43 +/- 0.30 log M, P=0.007) but not significant compared with that for U46619 (-5.81 +/- 0.11, P>0.05). Pretreatment with aprikalim depressed the contraction by phenylephrine from 140.6 +/- 27.6% to 49.3 +/- 14.1% (P=0.002) and shifted the EC50 11.0-fold higher in rings treated with 1 microM aprikalim (P=0.007). Treatment of aprikalim did not significantly reduce the K+ and U46619-induced contraction (P>0.05) but shifted the concentration-contraction curves rightward (2.8-fold higher for K+, P<0.05 and 2.2-fold higher for U46619, P<0.05). CONCLUSIONS: This study demonstrates that aprikalim has vasorelaxant effects in human conduit arteries used as coronary artery bypass grafts contracted by a variety of vasoconstrictors and this effect is vasoconstrictor-selective with greater potency for alpha1-adrenoceptor agonists than for depolarizing agent K+. These findings provide information on the possible use of this KCO in various clinical settings.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Comparison of nitroprusside and nitroglycerin in inhibition of angiotensin II and other vasoconstrictor-mediated contraction in human coronary bypass conduits.

AIMS: To compare the effect of nitroprusside (SNP) and nitroglycerin (NTG) on angiotensin II (ANGII), endothelin-1 (ET-1), and alpha1-adrenoceptor (phenylephrine, PE)-mediated contraction in internal mammary artery (IMA). METHODS: Human IMA segments (n=120) taken from 37 patients were studied. Concentration-relaxation curves for SNP and NTG were established in IMA precontracted with these vasoconstrictors. Concentration-contraction curves were also constructed in IMA rings incubated with SNP and NTG (0.1 and 1 microM) for 10 min. RESULTS: Both SNP and NTG caused full relaxation with similar EC50s except NTG was four-fold more potent than SNP in PE-induced contraction (-7.92 +/- 0.06 vs -7.32 +/- 0.2 log M, mean +/- s.e. mean, P<0.01; 95% confidence interval for the difference of the means: 0.19, 1.01 log M). Pretreatment with SNP (0.1 and 1 microM) significantly depressed the contraction by ANGII from 56.6 +/- 7.7% (of 100 mM K+-contraction) to 18.3 +/- 8.6% and 3.9 +/- 2.1% (P=0.0001). In four rings treated with SNP, the contraction to ANGII was abolished whereas NTG did not depress ANGII-mediated contraction. Pretreatment with SNP (1 microM), but not NTG, significantly depressed the magnitude of the PE-induced contraction from 4.7 +/- 1.2 to 1.7 +/- 0.4 g (P<0.05). Treatment with both SNP and NTG significantly increased the EC50 (-5.09 +/- 0.17 log M, P=0.0007 for SNP and -5.40 +/- 0.06 log M, P=0.02 for NTG). Pretreatment with SNP did not significantly change either the magnitude or the EC50 of the ET-1-induced contraction. CONCLUSIONS: SNP may be advantageous compared with NTG in preventing coronary arterial graft contraction. However, once grafts have constricted to ANGII, alpha1-adrenoceptor agonists, and ET-1, NTG may be only marginally advantageous.

Adrenergic alpha-Agonists↗
PubMed1997

Coronary endothelial function in open heart surgery.

1. During open heart surgery, the heart is arrested and protected by hyperkalaemic cardioplegia. The coronary endothelium may be damaged by ischaemia-reperfusion and cardioplegia. Subsequently, this may affect cardiac function immediately after cardiac surgery and cause mortality or morbidity. 2. Our studies have investigated coronary endothelial function after exposure to hyperkalaemia (K+ 20 or 50 mmol/L). Endothelium-dependent relaxation and hyperpolarization of the coronary smooth muscle and intracellular free calcium concentration in the endothelial cell were measured with regard to K+ exposure. 3. Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation to A23187, bradykinin, and substance P in the presence of either U46619 (10 nmol/L)- or K+ (25 mmol/L)-induced contraction was reduced after exposure to either 20 or 50 mmol/L K+. 4. The hyperpolarization of the membrane potential in response to the endothelium-derived relaxing factor (EDRF) stimuli was also reduced by exposure to K+. 5. The intracellular free calcium concentration remained unchanged after exposure to hyperkalaemia. 6. We conclude that the EDHF-mediated coronary endothelial function is impaired after exposure to hyperkalaemic cardioplegia. The impairment of this function is due to the changed effect of EDHF on the smooth muscle cell, probably through partially depolarizing the membrane and affecting K+ channels rather than alteration of its biosynthesis/release in the endothelial cell. It may be of use to search for a new cardioplegia that preserves this endothelial function during open heart surgery.

Animals↗
PubMed1996

Use of verapamil and nitroglycerin solution in preparation of radial artery for coronary grafting.

BACKGROUND: The radial artery (RA) has been used as an alternative arterial graft for coronary artery bypass grafting. This artery has been reported to be spastic; therefore, use of spasmolytic drugs (vasodilators) during the preparation of the RA is recommended. The combination of calcium antagonists and nitroglycerin (verapamil plus nitroglycerin, VG solution) has been suggested to be effective in other bypass grafts. This study was designed to investigate (1) the effect of the VG solution during preparation of the RA for coronary artery bypass grafting and (2) whether the effect would last for a prolonged period after topical use. METHODS: Ring segments of the RA taken from coronary artery bypass grafting patients were studied in organ chambers at a physiologic pressure. The relaxation effect of VG (30 mumol/L verapamil and 30 mumol/L nitroglycerin, n = 5) or papaverine (30 mumol/L, n = 5) was recorded in K+ (25 mmol/L potassium chloride)-precontracted RA segments. Other segments taken from the RA were treated (n = 5) or not treated (n = 20, as the control) with the VG solution for 45 minutes before used for coronary artery bypass grafting. Both the VG-treated and nontreated segments were immersed in oxygenated Krebs solution and stored in a refrigerator at 4 degrees C for 24 hours. The contraction force to 100 mmol/L K+ was compared between the two groups. RESULTS: The VG solution induced more rapid relaxation than papaverine (p < 0.05 from the first to the ninth minute). After 10 minutes, both solutions induced full relaxation. The contraction to K+ (100 mmol/L) in rings treated with VG solution for 45 minutes during operation was almost abolished 24 hours later (0.86 +/- 0.1 g). In contrast, the control segments (n = 20) taken from nontreated RA contracted with K+ to high force (5.0 +/- 0.6 g; p < 0.001). CONCLUSIONS: The present study suggests that the combination of verapamil and nitroglycerin may provide a rapid onset, a complete relaxation, and a long-lasting vasorelaxant effect when used to prepare the RA for grafting. This study adds a new method to prevent RA spasm during coronary artery bypass grafting.

Coronary Artery Bypass↗
PubMed1996

Hyperkalemia alters endothelium-dependent relaxation through non-nitric oxide and noncyclooxygenase pathway: a mechanism for coronary dysfunction due to cardioplegia.

BACKGROUND: Reported results of hyperkalemia (cardioplegia or organ preservation solutions) on endothelial function are contradictory. The endothelium-dependent relaxation is related to three major mechanisms: cyclooxygenase, nitric oxide, and endothelium-derived hyperpolarizing factor (K+ channel related). The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through non-nitric oxide and noncyclooxygenase pathways. METHODS: Porcine coronary artery rings (5 to 10 in each group) were studied in organ chambers under physiologic pressure. After incubation with 20 or 50 mmol/L K+ for 1 hour, the response to substance P, an endothelium-dependent vasorelaxant peptide, in K+ (25 mmol/L)-induced contraction was studied in the presence of the cyclooxygenase inhibitor indomethacin (7 mumol/L), the nitric oxide biosynthesis inhibitor NG-nitro-L-arginine (L-NNA) (300 mumol/L), or the adenosine triphosphate-sensitive K(+)-channel blocker glybenclamide (3 mumol/L) in comparison with control arteries (69.8 +/- 4.6% of K+ contraction). RESULTS: Without exposure to hyperkalemia, indomethacin (with or without glybenclamide) did not alter but L-NNA significantly reduced the relaxation (39.7% +/- 3.7%, p < 0.001). After exposure to K+, the indomethacin- and L-NNA-resistant relaxation was further reduced (7.4% +/- 3.2% for 20 mmol/L K+, p < 0.0001; or 13.5% +/- 8.4% for 50 mmol/L K+, p < 0.05, compared with rings without exposure), whereas the indomethacin- and glybenclamide-resistant relaxation was not altered. Incubation with hyperkalemia (50 mmol/L) also significantly reduced the sensitivity (increased EC50) of the indomethacin- and L-NNA-resistant relaxation (-9.75 +/- 0.06 versus -9.33 +/- 0.04 log M, p < 0.01). CONCLUSIONS: Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation. Our study may suggest a new mechanism of coronary dysfunction after exposure to hyperkalemia and open a new area for protection of coronary endothelium in cardiac surgery and for organ preservation in transplantation surgery.

Animals↗
PubMed1996

Aortic valve replacement in elderly patients: influence of concomitant coronary grafting on late survival.

BACKGROUND: Aortic valve replacement (AVR) has been an accepted therapy for elderly patients (> 70 years) with aortic valve disease. This study was designed to investigate the determinants of survival after the implantation of aortic valve prostheses, with emphasis on the effect of concomitant coronary artery bypass grafting on survival. METHODS: From November 1964 to July 1994,963 elderly patients underwent isolated AVR. Long-term survival was investigated in 877 patients (70 to 94 years) who survived operation, with 92% follow-up completeness (mean +/- standard deviation, 4.5 +/- 3.9 years; maximum, 20.1 years; total, 3,920.2 patient-years), by univariate and multivariate analyses. RESULTS: Actuarial survival was 38.1% +/- 2.8% at 10 years, 17.8% +/- 3.0% at 15 years, and 9.0% +/- 3.1% at 20 years. Eight variables (age, sex, body surface area [less or greater than 1.7 m2], period of operation, type of prosthesis, size of prosthesis, re-replacement, and concomitant coronary artery bypass grafting) were investigated with regard to long-term survival by the Kaplan-Meier method. Age, sex, and body surface area were significant. Multivariate analysis revealed that older age (p = 0.0005) and male sex (p = 0.0001) were independent variables that determined long-term survival. CONCLUSIONS: Elderly patients may have satisfactory long-term results after AVR. Age and sex are independent determinants. Other factors (such as concomitant coronary artery bypass grafting and type of prosthesis) did not independently influence long-term survival. Coronary revascularization in elderly patients with coronary disease undergoing AVR may lead to a long-term survival similar to that in patients without coronary disease undergoing AVR.

Actuarial Analysis↗
PubMed1996

Is referral source a risk factor for coronary surgery? Health maintenance organization versus fee-for-service system.

We began performing coronary artery bypass grafting for a large health maintenance organization (HMO) in 1974, as the sole provider of their cardiac surgery. The outcomes of our HMO group of patients were compared with those of our patients treated on a fee-for-service (FFS) basis. The HMO system entails preintervention and multidisciplinary screening conferences and is devoid of self-referral and personal financial incentives. Since 1985, the operative mortality for HMO patients has been consistently lower than for FFS patients. There were 8483 operations during this study period: 3168 (37%) were in the HMO group, with an overall operative mortality of 2.7%, and 5315 (63%) were in the FFS group, with an operative mortality of 4.6% (p=0.00002). This difference was investigated with univariate and multivariable analyses. Sixteen factors were found to univariately affect the risk of operative mortality; for five of these risk correlates there was a significant maldistribution between the HMO and FFS patients. Logistic regression was used to explore the influence of this imbalance in risk factors. The model found seven independent risk factors (left ventricular failure, emergency coronary bypass, redo bypass, nonuse of the internal thoracic artery, unstable angina, age, and diabetes) that significantly affected operative mortality. The FFS group variable closely approached independent risk significance at p=0.059. This multivariable model explained only one third of the observed differences in actual mortality between the HMO and FFS groups. The system-wide angioplasty/coronary bypass ratio, which could not be used in a patient-specific model, was 0.6 in the HMO system and 1.5 in the FFS group. Other factors related to the operating structure of a mature, large HMO may account for the remainder of the difference. The HMO referral system, through a powerful selection process, resulted in fewer emergencies, redo bypass operations, and catheterization complications that, in turn, yielded lower operative mortality than a noncoordinated FFS system of cardiovascular management.

Angioplasty, Balloon, Coronary↗
PubMed1996

Inhibition of vasoconstriction by phosphodiesterase III inhibitor milrinone in human conduit arteries used as coronary bypass grafts.

We wished to determine the effect of phosphodiesterase III (PDE III) inhibitor milrinone on human arteries used as coronary bypass grafts. Human internal mammary artery segments (IMA, n = 109) taken from 25 patients were studied. Concentration-relaxation curves for milrinone were established in IMA precontracted with four vasoconstrictors [K+, endothelin-1 (ET-1), U46619, and phenylephrine (PE)]. In IMA rings incubated with therapeutic plasma concentrations of milrinone (7 and 70 microM) for 10 min, concentration-contraction curves for the four vasoconstrictors were constructed. Milrinone caused a complete relaxation in U46619, ET-1, PE (100%), or K+ (97.7%)-precontracted IMA. The EC50 value was higher against K+ (-5.31 +/- 0.27 log M) than PE (-6.20 +/- 0.25 log M, p = 0.036) or endothelin-1 (-6.41 +/- 0.28 log M, p = 0.018). Pretreatment with milrinone decreased the contraction induced by ET-1 from 186.0 +/- 23.3 to 66.9 +/- 9.6% (p = 0.002) and that induced by PE from 140.6 +/- 27.6 to 54.1 +/- 7.0% (p = 0.03) and shifted the EC50 7.6-fold higher (p = 0.003). Treatment of milrinone reduced the K+ and U46619 contraction (p < 0.05) at lower concentrations (between 10 and 80 mM for K+ and -8.5 and -7.5 log M for U46619) and shifted the concentration-contraction curves rightward (2.56-fold higher for K+, p < 0.0001; 3.18-fold higher for U46619, p = 0.007). Denudation of endothelium did not affect the milrinone-induced relaxation. These results demonstrate that milrinone is a potent vasodilator of human conduit arteries used as coronary bypass grafts and may have a slight selectivity with greater potency to receptor stimulants than to the depolarizing agent K+. The results may prove a particular indication for milrinone for use in patients receiving arterial grafts for coronary bypass.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Potential greater than additive vasorelaxant actions of milrinone and nitroglycerin on human conduit arteries.

1. The mechanism of vasorelaxation for phosphodiesterase III inhibitors is mediated by increase of cAMP whereas for nitrovasodilators, cGMP. The purpose of this study was to test the hypothesis that the phosphodiesterase III inhibitor milrinone and nitroglycerin (NTG) may have greater than additive effects in human arteries. 2. Internal mammary artery segments (IMA, n = 90) taken from 23 patients were studied in organ chambers. The effect of milrinone (3 microM), NTG (10 nM), or the combination was tested in IMA rings precontracted with potassium (K+, 25 mM) or U46619 (10 nM). Concentration-contraction curves for K+ or U46619 were established in other rings treated with milrinone (70 microM), NTG (0.1 microM), or the combination for 10 min. 3. In K(+)-induced contraction, the combination produced more relaxation (45.4%) than did either milrinone (7.9%, P < 0.05) or NTG (3.8%, P < 0.05) alone. This relaxation was significantly more than the theoretical overadditive effect (P < 0.05). Similar results were seen in U46619-induced contraction (94.1% by the combination vs 70.7% by milrinone, P < 0.05, or 36.1% by NTG, P < 0.05). Pretreatment with the combination depressed contraction to a higher extend compared with milrinone alone (P < 0.05) for the K(+)-induced contraction and to NTG alone (P < 0.05) in U46619-induced contraction. Treatment with the combination also shifted EC50 rightward and this shift was significantly more than that caused by treatment with NTG alone (P < 0.05). 4. We conclude that there is a greater than additive vasorelaxant effect of PDE III inhibitors and nitrovasodilators in human conduit arteries. This effect may be beneficial to patients undergoing coronary artery bypass grafting and to other patients requiring these vasodilators. Reduced doses of the vasodilators in concentration may be sufficient to produce vasodilatation similar to that produced by either of them alone at higher concentrations.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Hyperkalemia alters EDHF-mediated hyperpolarization and relaxation in coronary arteries.

Hyperkalemic solutions are widely used to preserve organs for transplantation and for cardiac surgery. The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through a non-nitric oxide (NO) pathway, since preliminary studies have shown that the NO pathway may not be affected. Porcine coronary artery rings were studied in organ chambers. After incubation with 20 or 50 mM K+ for 1 h, the indomethacin- and NG-nitro-L-arginine+ (L-NNA)-resistant relaxation induced by A23187 or bradykinin, which could be further inhibited by tetraethylammonium but not glibenclamide, was significantly reduced. Incubation with hyperkalemia also significantly increased the concentration eliciting 50% of the maximal response to A23187 and bradykinin. A23187-induced hyperpolarization of the membrane potential was significantly reduced by hyperkalemic incubation. However, 1-h incubation with hyperkalemia does not affect the endothelial Ca2+ concentration. We conclude that exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant endothelium-dependent relaxation and endothelium-dependent hyperpolarization. This reduction in the relaxation and hyperpolarization is related to the endothelium-derived hyperpolarizing factor by affecting its effect on the smooth muscle cell, probably through partially depolarizing the membrane, and the Ca2(+)- activated K+ channels rather than by affecting its biosynthesis and/or release in the endothelial cell. Our study may suggest a new mechanism for coronary dysfunction after exposure to hyperkalemic cardioplegia and organ preservation solutions.

Animals↗
PubMed1995

Strategies for repair of congenital heart defects in infants without the use of blood.

Eleven infants and children with a body weight of less than 10 kg (median weight, 6.8 kg) whose parents were Jehovah's Witnesses underwent repair (n = 10) or palliation (n = 1) of congenital heart defects without the use of blood products and with (n = 9) or without (n = 2) cardiopulmonary bypass (CPB). In 1 neonate (weight, 3.2 kg) with critical aortic stenosis, moderate hypothermia and a 3.5-minute period of inflow occlusion and circulatory arrest allowed an aortic valvotomy; in another patient (weight, 7.0 kg) with tricuspid and pulmonary atresia, transposition of the great arteries, and persistent left superior vena cava, a bilateral bidirectional cavopulmonary shunt procedure was performed without CPB. Use of heparin-bonded tubing allowed reduction of the initial dose of heparin sodium to 1 mg/kg. Tissue perfusion and oxygenation on bypass were adequate, as evidenced by a mean lowest pH of 7.38 +/- 0.09 and a mean lowest venous oxygen tension of 65.0 +/- 36.2 mm Hg. Although the mean postoperative hematocrit (Hct) was lower than the mean preoperative Hct (p < 0.05, analysis of variance and Scheffe's F test), the Hct within 2 hours after CPB was restored to a value (mean Hct, 27.5% +/- 1.0%) between the preoperative Hct (mean value, 42.7% +/- 3.5%) and the lowest Hct on CPB (mean value, 18.4% +/- 1.4%). The Hct at discharge was 31.8% +/- 1.1%. The median postoperative blood loss was 9 mL/kg. There was no perioperative mortality. The median stay in the intensive care unit and the hospital was 2 days and 6 days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Loss, Surgical↗