Neutrophil inhibition contributes to cardioprotection by postconditioning.

BACKGROUND: Postconditioning (postcon) reduces infarct size, myocardial superoxide ((•)O(2)) generation, and neutrophil (PMN) accumulation. It is unknown whether inhibition of PMNs influence cardioprotection by postcon. The present study tested the following hypotheses: (1) myocardial salvage by postcon is modified by inhibition of PMNs and (2) postcon directly inhibits PMN (•)O(2) generation. METHODS: For hypothesis 1, a deductive approach was used to determine infarct size in vivo with and without PMNs in rats, and for hypothesis 2, blood sampled from the anterior interventricular vein (AIV) in a canine model was used. Protocol 1: anesthetized rats, subjected to 30 min of coronary artery occlusion and 3 h of reperfusion, were randomized to control (n = 13), postcon (n = 13), PMN-depletion: (n = 9), and postcon in PMN-depleted rats (n = 9). Protocol 2: blood was sampled at baseline, 2 h and 24 h from the AIV, draining the area at risk (AAR) in anesthetized dogs with 60 min coronary occlusion ± postcon; whole blood was analyzed for (•)O(2) by luminol-enhanced chemiluminescence. RESULTS: Postcon and PMN depletion reduced infarct size (42.6 ± 2.1%, P < 0.05 vs. control, and 43.9 ± 3.0%, P < 0.05 vs. control, respectively) vs. control (58.8 ± 0.9%), with no further decrease with postcon in PMN-depleted rats (37.2 ± 2.9%, P = 0.34 vs. postcon). PMN accumulation in AAR was less in postcon (21.2 ± 0.3%, P < 0.05 vs. control) and PMN-depleted (9.4 ± 0.3%, P < 0.05 vs. control) vs. control (30.5 ± 1.2%), with a further decrease in the postcon + PMN depletion group (5.4 ± 0.6%, P < 0.05 vs. control). In dogs, (•)O(2) release by PMNs increased at 2 h and 24 h of R, which was reduced to baseline levels by postcon. CONCLUSIONS: These data imply PMN involvement in cardioprotection by postconditioning.

All-blood (miniplegia) versus dilute cardioplegia in experimental surgical revascularization of evolving infarction.

BACKGROUND: The advantages of blood cardioplegia include the oxygen-carrying capacity, superior oncotic and buffering properties, and endogenous antioxidants contained in blood. However, the partial dilution of blood in 4:1 (blood:crystalloid) cardioplegic solutions may nullify these advantages and progressively dilute blood during continuous retrograde delivery. This study tested the hypothesis that all-blood (66:1) cardioplegia provides superior myocardial protection compared with dilute (4:1) cardioplegia delivered in a continuous retrograde modality during surgical reperfusion of evolving myocardial infarction. METHODS AND RESULTS: After 60 minutes of left anterior descending coronary artery (LAD) occlusion, anesthetized canines were placed on cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group) or dilute blood cardioplegia (Dil group). After cross clamping, arrest was induced with 5 minutes of tepid (30 degrees C) antegrade potassium all-blood or dilute blood cardioplegia and maintained with tepid retrograde coronary sinus cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of arrest, simulating revascularization. The cardioplegia hematocrit for the Dil group was lower than that for the AB group (7+/-1% versus 12+/-2%, P<0.05); at the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab group (15+/-1% versus 20+/-1%, P<0.05). Infarct size (triphenyltetrazolium chloride staining) was comparable between the AB and Dil groups (29.6+/-2.9% versus 30.3+/-3.9% of area at risk), and there was no difference in area-at-risk myocardium systolic shortening (by sonomicrometry, -0.3+/-1% versus -0.4+/-1%). Tissue edema after bypass tended to be greater in the Dil group compared with the AB group in the heart (82+/-0% versus 81+/-1%), lung (79+/-1% versus 78+/-1%), liver (75+/-1% versus 74+/-0%), and skeletal muscle (76+/-1% versus 73+/-2%) and was significantly greater in the duodenum (80+/-1% versus 79+/-1%, P<0.05) and kidney (82+/-1% versus 79+/-1%, P<0.05). Postexperimental endothelial function (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil group (59+/-6% versus 77+/-5%, P<0.05). CONCLUSIONS: Both all-blood cardioplegia and dilute cardioplegia have disadvantages, but these do not have an impact on the pathogenesis of infarct size or recovery of regional contractile function.

Glutathione reverses endothelial damage from peroxynitrite, the byproduct of nitric oxide degradation, in crystalloid cardioplegia.

BACKGROUND: NO has been advocated as an adjunct to cardioplegia solutions. However, NO undergoes a rapid biradical reaction with superoxide anions to produce peroxynitrite (ONOO(-)). ONOO(-) in crystalloid cardioplegia solution induces injury to coronary endothelium and to systolic function after cardioplegia and reperfusion. However, ONOO(-) may be degraded to less lethal or cardioprotective intermediates with glutathione (GSH) in reactions separate from its well known antioxidant effects. We hypothesized that GSH detoxifies ONOO(-) and reverses defects in endothelial function and systolic function when present in crystalloid cardioplegia. METHODS AND RESULTS: In anesthetized dogs on cardiopulmonary bypass, a 45-minute period of global normothermic ischemia was followed by 60 minutes of intermittent cold crystalloid cardioplegia (Plegisol) and 2 hours of reperfusion. The cardioplegia solution contained 5 micromol/L authentic ONOO(-); catalase was included to attenuate the potential antioxidant effects of GSH and to unmask the effects on ONOO(-). In 1 group (CP+GSH, n=5), the cardioplegia contained 500 micromol/L GSH, whereas 1 group received crystalloid cardioplegia without GSH (CCP, n=6). There were no group differences in postcardioplegia left ventricular systolic function (end-systolic pressure-volume relation, impedance catheter: CCP 10.0+/-2.4 versus CP+GSH 10.6+/-1.3 mm Hg/mL) or diastolic chamber stiffness (ss-coefficient: CCP 0.35+/-0.2 versus CP+GSH 0.31+/-0.18). Myocardial neutrophil accumulation (myeloperoxidase activity) was attenuated in CP+GSH versus CCP (2.2+/-0.7 versus 5.4+/-1.2, P:<0.05). In postexperimental coronary arteries, maximal endothelium-dependent relaxation was greater in CP+GSH than in CCP (118+/-6% versus 92+/-5%, P:<0.05), with a smaller EC(50) value (-7. 10+/-0.05 versus -6.98+/-0.03, respectively, P:<0.05). Smooth muscle relaxation was complete in both groups. The adherence of neutrophils to postexperimental coronary arteries as a measure of endothelial function was less in CP+GSH than in CCP (98+/-18 versus 234+/-36 neutrophils/mm(2), P:<0.05). Nitrosoglutathione, a byproduct of the reaction between ONOO(-) and GSH, was greater in CP+GSH than in CCP (4.1+/-2.3 versus 0.4+/-0.2 microg/mL, P:<0.05). CONCLUSIONS: GSH in crystalloid cardioplegia detoxifies ONOO(-) and forms cardioprotective nitrosoglutathione, resulting in attenuated neutrophil adherence and selective endothelial protection through the inhibition of neutrophil-mediated damage.

Vasodilator drug effects on internal mammary artery and saphenous vein grafts.

The internal mammary artery is a dynamic conduit used for myocardial revascularization in which potential exists for spasm as well as for vasodilation. This study investigated vasodilator drug effects on the mammary artery using nitroprusside and nitroglycerin in vitro to measure the inhibition of contraction of human internal mammary artery and in vivo to examine blood flow through a canine mammary artery. In the in vitro study, ring segments of human internal mammary arteries were suspended on strain gauges in muscle baths containing 37 degrees C Krebs solution for measurement of isometric tension in vitro. Arterial contraction was stimulated with 70 mM potassium and 10 microM norepinephrine, and inhibition of contraction by vasodilators was measured. Nitroprusside was more potent and effective than was nitroglycerin in inhibiting potassium and norepinephrine contraction. The in vivo study utilized a canine (n = 8) right heart bypass preparation that allowed precise control of cardiac output, blood pressure and heart rate, which were maintained constant. The internal mammary artery graft and the saphenous vein graft perfused the same coronary artery bed. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 min of drug infusion (1 microgram/kg per min). Nitroglycerin significantly increased mammary artery flow 36 +/- 13%, whereas nitroprusside significantly decreased it 12 +/- 2%. Saphenous vein grafts responded differently; graft blood flow decreased with nitroglycerin and increased with nitroprusside. Thus, although nitroprusside was more effective than nitroglycerin in inhibiting mammary artery contraction in vitro, it decreased internal mammary artery graft flow measured in vivo. Nitroglycerin had the opposite effect, increasing mammary graft flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight-year mortality in the Emory Angioplasty versus Surgery Trial (EAST)

OBJECTIVES: To evaluate the long-term outcome of patients randomized to coronary bypass surgery or coronary angioplasty. BACKGROUND: The Emory Angioplasty versus Surgery Trial (EAST) is a single center randomized comparison of a strategy of initial coronary angioplasty (n = 198) or coronary bypass surgery (n = 194) for patients with multivessel coronary artery disease. The primary end point (death, myocardial infarction or a large ischemic defect at 3 years) was not different, and repeat revascularization was significantly greater in the angioplasty group. Subsequently, the National Heart, Lung and Blood Institute supported a five-year extension of the trial. METHODS: After the three year anniversary visit, annual questionnaires, telephone contact and examination of medical records were accomplished until death or the eight year anniversary in 100% of the patients surviving at 3 years. RESULTS: Survival at 8 years is 79.3% in the angioplasty group and 82.7% in the surgical group (p = 0.40). Patients with proximal left anterior descending stenosis and those with diabetes tended to have better late survival with surgical intervention although not reaching statistical significance. After the first 3 years, repeat interventions remained relatively equal for both treatment groups. CONCLUSIONS: Long-term survival is not significantly different between angioplasty and surgery, and late (three to eight year) revascularization procedures were infrequent. Patients without treated diabetes had similar survival in both groups.

Outcome of coronary bypass surgery versus coronary angioplasty in diabetic patients with multivessel coronary artery disease.

OBJECTIVES: This study sought to compare the outcome of percutaneous transluminal coronary angioplasty (PTCA) (n = 834) and coronary artery bypass graft surgery (CABG) (n = 1805) in diabetic patients with multivessel coronary disease from an observational database. BACKGROUND: There is concern about selection of revascularization in diabetic patients with multivessel coronary artery disease. METHODS: Data were collected prospectively and entered into a computerized database. Follow-up was by letter or telephone or additional events resulting in readmission. RESULTS: After CABG there were more in-hospital deaths (0.36% vs. 4.99%, p < 0.0001) and a trend toward more Q wave myocardial infarctions than after PTCA. Five- and 10-year survival rates were 78% and 45% after PTCA and 76% and 48% after CABG, respectively (p = 0.47). At 5 and 10 years, insulin-requiring patients had lower survival rates of 72% and 31% after PTCA and 70% and 48% after CABG, respectively (p = 0.54). Multivariate correlates of long-term mortality were older age, low left ventricular ejection fraction, heart failure and hypertension. In the total group, insulin requirement was a correlate of long-term mortality. For the total group, choice of therapy had a multivariate hazard ratio close to 1. In the insulin-requiring subgroup, the multivariate hazard ratio was 1.35 (95% confidence interval 1.01 to 1.79) for PTCA versus CABG. Corrected for baseline differences, 5- and 10-year survival rates were 68% and 36% after PTCA and 75% and 47% after CABG, respectively, in the insulin-requiring subgroup. Nonfatal events were more common after PTCA, especially additional revascularization. CONCLUSIONS: This study reveals a high incidence of events in diabetic patients and raises further questions about angioplasty in insulin-requiring diabetic patients with multivessel disease.

Comparative study of AMP579 and adenosine in inhibition of neutrophil-mediated vascular and myocardial injury during 24 h of reperfusion.

OBJECTIVE: The purpose of this study was to compare protective effects of AMP579 and adenosine (Ado) at reperfusion (R) on inhibition of polymorphonuclear neutrophil (PMN) activation, PMN-mediated injury to coronary artery endothelium, and final infarct size. METHODS: In anesthetized dogs, 1 h of left anterior descending coronary artery occlusion was followed by 24 h R and drugs were administered at R. Control (n=8, saline control), AMPI (n=7, AMP579, 50 microg/kg i.v. bolus followed by 3 microg/kg/min for 2 h), AMPII (n=7, AMP579, 50 microg/kg i.v. bolus), AMPIII (n=7, AMP579, 3 microg/kg/min i.v. for 2 h), and Ado (n=7, adenosine, 140 microg/kg/min i.v. for 2 h). RESULTS: AMP579 in vitro directly inhibited superoxide radical (O(-)(2)) generation (nM/5x10(6) PMNs) from PMNs dose-dependently (from 17+/-1* at 10 nM to 2+/-0.2* at 10 microM vs. activated 30+/-2). However, inhibition of O(-)(2) generation by Ado at each concentration was significantly less than for AMP579. The IC(50) value for AMP579 (0.09+/-0.02 microM) on O(-)(2) generation was significantly less than that of Ado (3.9+/-1. 1 microM). Adherence of unstimulated PMN to postischemic coronary artery endothelium (PMNs/mm(2)) was attenuated in AMPI and AMPIII vs. Control (60+/-3* and 58+/-3* vs. Control 110+/-4), while Ado partially attenuated PMN adherence (98+/-3*). Accordingly, endothelial-dependent vascular relaxation was significantly greater in AMPI and AMPIII vs. Ado. At 24 h R, myocardial blood flow (MBF, ml/min/g) in the area at risk (AAR), confirmed by colored microspheres, in AMPI and AMPIII was significantly improved (0.8+/-0. 1* and 0.7+/-0.1* vs. Control 0.3+/-0.04). Infarct size (IS, TTC staining) in AMPI and AMPIII was significantly reduced from 38+/-3% in Control to 21+/-4%* and 22+/-3%*, respectively, confirmed by lower plasma creatine kinase activity (I.U./g protein) in these two groups (27+/-6* and 32+/-2* vs. 49+/-3). Cardiac myeloperoxidase activity (MPO, Abs/min) in the AAR was significantly reduced in AMPI and AMPIII vs. Control (36+/-11* and 35+/-10* vs. 89+/-10). However, changes in MBF, IS and MPO were not significantly altered by Ado. CONCLUSIONS: These data suggest that continuous infusion of AMP579 at R is more potent than adenosine in attenuating R injury, and AMP579-induced cardioprotection involves inhibition of PMN-induced vascular and myocardial tissue injury. *P<0.05 vs. Control.

Reperfusion induces myocardial apoptotic cell death.

OBJECTIVE: The purpose of the present study was to investigate whether apoptosis is triggered during ischemia (I) and reperfusion (R) and whether I/R-induced apoptosis is correlated with changes in expression of Bcl-2 and Bax. METHODS: Anesthetized open-chest dogs were divided into two groups. Group I: 7 h of permanent I without R (PI, n = 7); Group II: 60 min I followed by 6 h R (I/R, n = 8). Apoptosis was identified as "DNA ladder" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end labeling (TUNEL) assay. RESULTS: Collateral myocardial coronary blood flow during I, confirmed by colored microspheres was comparable in both groups. Although PI caused 72 +/- 5% infarct size, very few TUNEL-positive cells were detected in the necrotic area (0.2 +/- 0.1% of total normal nuclei), consistent with an absence of DNA laddering. In contrast, the appearance of TUNEL-positive cells was significantly displayed after 6 h R in the necrotic area in I/R group (26 +/- 4%, P < 0.001 vs. PI group), and DNA ladder occurred in all experimental animals, suggesting that myocardial apoptosis is primarily elicited by R. Densitometrically, Western blot analysis showed significant reduction in expression of Bcl-2 (16 +/- 1%) and increase in Bax (29 +/- 8%) after 6 h R in the necrotic area compared with normal tissue while expression of these two proteins was not changed in the PI group. Polymorphonuclear neutrophil (PMN) accumulation in the necrotic area determined either by immunohistochemistry with anti-CD18 antibody or by myeloperoxidase activity was significantly increased in the I/R group compared to the PI group (358 +/- 24 vs. 24 +/- 2, mm2 myocardium, P < 0.01) and (2.9 +/- 0.3 vs. 0.4 +/- 0.1, U/100 mg tissue, P < 0.01). There was a significant linear relationship between CD18-positive PMNs and TUNEL-positive cells (P < 0.05) in the I/R group. CONCLUSIONS: These results indicate that (1) PI without R did not induce apoptotic cell death, while two types of cell death, necrosis and apoptosis were found after I/R, (2) the Bcl-2 family may participate in early R-induced myocardial apoptosis, (3) PMN accumulation may play a role in the development of apoptosis.

Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart.

OBJECTIVE: Recent studies suggest that ischemic preconditioning (IPC) inhibits myocardial apoptosis after ischemia and reperfusion. This study tested the hypothesis that IPC reduces ischemia/reperfusion-induced myocardial apoptosis by inhibiting neutrophil (PMN) accumulation and altering expression of Bcl-2 and Bax proteins. METHODS: Eighteen rats were subjected to 30 min of left coronary artery occlusion followed by 180 min of reperfusion with IPC (5 min ischemia and 10 min of reperfusion, n = 10) or without IPC (n = 8). Myocardial apoptosis was detected histologically using the terminal transferase UTP nick end labeling (TUNEL) assay and confirmed by DNA ladder on agarose gel electrophoresis. PMN accumulation was detected immunohistochemically with anti-rat CD18 antibody (WT3) and expression of Bcl-2 and Bax proteins was analyzed using Western blot assay. RESULTS: IPC significantly decreased TUNEL positive cells (% total nuclei) in the ischemic zone from 28.6 +/- 2.8 to 3.4 +/- 0.9 (P < 0.05), consistent with the absence of DNA ladders in the IPC group. IPC significantly attenuated PMN accumulation (cells/mm2 myocardium) in the ischemic zone from 243 +/- 19 to 118 +/- 19 (P < 0.05). By regression analysis, there was a significant correlation between TUNEL positive cells and accumulated CD18 positive PMNs in the ischemic zone (r = 0.8, P < 0.001), which was shifted downward by IPC. Densitometrically, IPC significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein in the ischemic zone from 204 +/- 57% in the control group to 76 +/- 7% (P < 0.05), while the expression of Bcl-2 was not different from the non-ischemic zone in either group. CONCLUSION: These data suggest that ischemic preconditioning may reduce myocardial apoptosis by inhibiting PMN accumulation and down-regulating expression of Bax.

Evolution of regional ischemia distal to a proximal coronary stenosis: self-propagation of ischemia.

The temporal evolution of myocardial ischemia was studied in open chest dogs at constant preload, afterload and heart rate. In one group of animals, a variable circumflex arterial stenosis was used to maintain constant distal circumflex arterial hypotension (40 to 50 mm Hg). During a 3 hour period of stenosis, flow in the subendocardial fourth of the ischemic ventricular wall decreased from 0.22 to 0.09 ml/g per min (P less than 0.02), whereas subepicardial flow was not significantly changed. Local vascular resistance, therefore, doubled in the most ischemic area of myocardium. In a second group of animals in which proximal coronary stenosis was held constant and pressure varied, an ischemia-mediated increase in local vascular resistance was also demonstrated. In addition, a reciprocal relation was observed between changes in flow in the left anterior descending coronary region and changes in collateral flow to the region of the circumflex artery. A coronary steal mechanism and an ischemia-mediated resistance increase may be two means by which ischemia is self-propagating.

Significance of subendocardial S-T segment elevation caused by coronary stenosis in the dog. Epicardial S-T segment depression, local ischemia and subsequent necrosis.

A model of partial thickness ischemia has been developed using subendocardial S-T elevation without epicardial S-T elevation to detect partial thickness ischemia which is sufficient to cause subsequent necrosis. Subendocardial blood flow in this model (measured with radioactive microsphere techniques) may be reduced to 25 percent of normal (P less than 0.001) by coronary stenosis and tachycardia while subepicardial flow remains normal. Epicardial S-T depression seems to indicate reciprocally subendocardial S-T elevation as long as a layer of nonischemic epicardial muscle is present, but when ischemia becomes transmural, epicardial S-T elevation occurs. Regional pressure-flow relations were determined as distal coronary pressure was reduced at a constant aortic pressure, heart rate and cardiac output. These relations revealed remarkably effective autoregulation of epicardial blood flow concomitant with progressive subendocardial ischemia.

Frequency of repeat coronary bypass or coronary angioplasty after coronary artery bypass surgery using saphenous venous grafts.

This study examines the long-term frequency of reoperative coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) after CABG. The source of data was the clinical database at Emory University Hospitals. The population comprised 3,480 patients undergoing a first CABG between 1978 and 1981. Event-free survival was determined using the Kaplan-Meier method and determinants of survival with the Cox proportional-hazards model. The in-hospital mortality was 1.0% and 5-, 10- and 12-year survival was 91, 78 and 70%. The 5-, 10- and 12-year freedom from reoperative CABG was 98, 88 and 80%. The 5-, 10- and 12-year freedom from PTCA was 98, 91 and 85%. The 5-, 10- and 12-year freedom from either CABG or PTCA was 96, 81 and 69%. Younger patients had much higher incidences of repeat procedures. The yearly incidence of repeat procedures accelerated over time. These data reveal the ultimately palliative nature of revascularization for coronary artery disease.

Late follow-up after repair of left ventricular aneurysm and (usually) associated coronary bypass grafting.

This study assesses clinical and operative data (LV) aneurysm was repaired to determine factors that might predict in-hospital and long-term outcome. Long-term follow-up study was obtained in 296 of 298 patients undergoing LV aneurysm repair with or without coronary artery bypass grafting between 1974 and 1986. No patient had sustained a myocardial infarction within 2 weeks of surgery or was undergoing other concurrent cardiac surgery. The average age of the study patients was 57 +/- 9 years and the average ejection fraction was 35 +/- 13%. Ninety percent of the patients underwent concurrent bypass grafting, with an average of 2.2 +/- 1.3 grafts placed. Fourteen (5%) patients died in the hospital, with most deaths attributable to LV dysfunction. Advanced age and less extensive revascularization were correlates of in-hospital mortality. The 10-year survival was 57%, myocardial infarction-free survival 43%, and freedom from death, myocardial infarction and reoperative coronary surgery 41%. Advanced age, systemic hypertension, significant left main coronary artery narrowing and emergent operative status were multivariate correlates of long-term mortality. A low-risk population was defined by the absence of these risk factors, and high-risk by the presence of greater than or equal to 1 risk factors. The 10-year survival was 71% in the low-risk and 41% in the high-risk groups (p = .0006). The 10-year myocardial infarction free survival was 55% in the low-risk and 31% in the high-risk groups (p = 0.0017). LV aneurysm repair may be performed with acceptable in-hospital mortality, and the long-term risk may be stratified.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of coronary revascularization in patients on renal dialysis.

Previous retrospective studies showed high periprocedure mortality rate and poor outcome after percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) among renal dialysis patients. The purpose of this study was to compare mortality and clinical event rates in renal dialysis patients after PTCA or CABG. We identified 252 patients from the Emory Cardiovascular Database who were on dialysis and who received PTCA (122 patients) or CABG (130 patients) at Emory University Hospital and Crawford W. Long Hospital between March 1987 and December 1997. Baseline and angiographic characteristics, in-hospital, and 1-year outcome were compared between the 2 groups. Left main disease and 3-vessel coronary artery disease were significantly more common in the CABG group. There was a higher periprocedure and in-hospital mortality in the CABG group (6.9% vs 1.6%, p = 0.04). Patients in the PTCA group underwent repeat revascularization 11 times more frequently within 1 year (22% vs 2%). At 1 year, mortality was 23% in the PTCA group and 27% in the CABG group, with no statistical difference between the 2 groups. This nonrandomized comparison reveals that PTCA and CABG can be performed in selected renal dialysis patients with an acceptable in-hospital major complication rate; however, 1-year mortality remains high in dialysis patients after coronary revascularization. Therefore, attempts at improving outcome in dialysis patients should focus on the prevention and treatment of coronary artery disease before they require coronary revascularization.

Importance of complete revascularization in performance of the coronary bypass operation.

Cardiac Data Bank records of 1,238 patients with triple-vessel disease (greater than or equal to 50% diameter reduction) who had undergone coronary bypass surgery were reviewed and divided into 2 groups depending on whether complete (n = 773) or incomplete (n = 465) revascularization had been accomplished. Patients with complete revascularization had a higher incidence of a normal preoperative electrocardiogram than did patients with incomplete revascularization (23 versus 14%, respectively, p less than 0.0001). The ejection fraction for both completely and incompletely revascularized patients was good (m = 0.60 and 0.57, respectively). The mean number of grafts per patient for the 2 groups was 3.8 and 2.6 (p less than 0.0001). There was no significant difference between the 2 groups with regard to postoperative inotropic requirements (8 and 7%), ventricular arrhythmias (1.8 and less than 1%), necessity for intraaortic balloon pumping (1.6 and 1.5%, hospital mortality (1.2 and 2.8%), or myocardial infarction (4.3 and 4.8%). Survival at 5 years was significantly greater (p less than 0.001) in patients with complete (88.5%) than in those with incomplete revascularization (83.5%). Reemployment occurred more often in patients with complete (52%) than in those with incomplete revascularization (40%) (p less than 0.001), and more patients were free of angina after complete (70%) than after incomplete revascularization (58%) (p less than 0.0005). Long-term survival appeared to be mediated primarily through improved revascularization rather than through differences in left ventricular function.

Coronary surgery and coronary angioplasty in patients with two-vessel coronary artery disease.

There is uncertainty regarding the selection between coronary artery surgery and angioplasty in many patients with coronary artery disease, especially in those with 2-vessel disease. Whereas randomized trials will provide the best possible and most detailed data comparing therapy in these patients, clinical data bases may be used to provide a current perspective. The purpose of this study was to compare the long-term outcome of patients with 2-vessel coronary artery disease undergoing coronary surgery or angioplasty at Emory University hospitals in the years 1984 and 1985. Data on all patients with 2-vessel disease diagnosed at Emory University who underwent elective angioplasty or coronary surgery in the years 1984 and 1985 were compared. Categoric variables were analyzed by chi-square and continuous variables by unpaired t test. Survival was determined by the Kaplan-Meier method and differences in survival by the Mantel-Cox method. Determinants of survival were determined by Cox model analysis. There were 415 angioplasty patients and 454 surgical patients. Surgical patients were older and had more frequent systemic hypertension, diabetes mellitus, prior myocardial infarction, severe angina and congestive failure, and more significant narrowing in the left anterior descending coronary artery, totally occluded vessels and left ventricular dysfunction than did angioplasty patients. Complete revascularization was achieved more often in surgical patients. There was no difference in Q-wave myocardial infarction in the hospital. No angioplasty patient died compared with 1.1% of surgical patients (p = 0.03). Whereas 5-year survival was 93% in angioplasty patients and 89% in surgical patients (p = 0.11), there was no difference in risk-adjusted survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty or surgery for multivessel coronary artery disease: comparison of eligible registry and randomized patients in the EAST trial and influence of treatment selection on outcomes. Emory Angioplasty versus Surgery Trial Investigators.

The Emory Angioplasty versus Surgery Trial (EAST) showed that multivessel patients eligible for both percutaneous transluminal coronary angioplasty (PTCA) and coronary bypass surgery (CABG) had equivalent 3-year outcomes regarding survival, myocardial infarction, and major myocardial ischemia. Patients eligible for the trial who were not randomized because of physician or patient refusal were followed in a registry. This study compares the outcomes of the randomized and registry patients. Of the 842 eligible patients, 450 did not enter the trial. Their baseline features closely resembled those of the randomized patients and follow up was performed using the same methods. In the registry there was a bias toward selecting CABG in patients with 3-vessel disease (84%) and PTCA in patients with 2-vessel disease (54%). Three-year survival for the registry patients was 96.4%, which was better than the randomized patients, 93.4% (p = 0.044). Angina relief in the registry was equal for CABG and PTCA patients and was better for the PTCA registry (12.4%) than PTCA randomized patients (19.6%) (p = 0.079). Thus, the registry confirms that EAST is representative of all eligible patients and does not represent a low-risk subgroup. Since baseline differences were small, improved survival in the registry may be due to treatment selection. Physician judgment, even in patients judged appropriate for clinical trials, remains a potentially important predictor of outcomes.

Drip retrograde coronary sinus perfusion for myocardial protection during aortic cross-clamping.

Moderate hypothermia is one of the methods utilized for myocardial protection when the aortic root is cross-clamped but not opened. A combination of low-pressure, low-flow retrograde coronary sinus perfusion (RCSP) with oxygenated blood at moderate hypothermia (29 degrees C.) was demonstrated to yield significantly better protection to left ventricular function in dogs than does moderate hypothermia alone. Ventricular function was recorded before and after 1 hour of aortic cross-clamping at identical preloads and heart rates. Aortic pressure was returned to a level as close to base line as possible by constriction of the descending aorta. The average mean aortic pressure of the animals perfused retrograde at 29 degrees C. was returned to within 4 per cent of base line. By contrast, in the animals protected with moderate hypothermia alone, the pressure could be returned only to a level which was 37 per cent lower than base line. In animals protected with moderate hypothermia alone, cardiac output dropped 62 per cent, left ventricular stroke work (LVSW) 75 per cent, and peak dp/dt 44 per cent. In the animals protected with RCSP and moderate hypothermia, the cardiac output dropped 6 per cent, LVSW 9 per cent, and peak dp/dt 5 per cent. The differences in the changes noted between these two groups were significant for LVSW and dp/dt at a level of p less than 0.01 and for cardiac output and aortic pressure at a level of p less than 0.05. These results suggest that RCSP may be indicated when moderate hypothermia is otherwise chosen to be the sole source of myocardial protection.

Coronary bypass surgery: is the operation different today?

Patients undergoing coronary bypass grafting have undergone an evolution in recent years. To document this change, we analyzed two groups of patients in 1981 (n = 1586) and 1987 (n = 1513) to document preoperative and postoperative variables important in determining immediate morbidity and mortality after isolated coronary bypass. Between 1981 and 1987, patients were found to be older (greater than or equal to 70 years, 8.7% versus 21.8%, p less than 0.0001), more often diabetic (15% versus 24%, p less than 0.0001), have a greater prevalence of triple vessel disease (14.5% versus 46.1%, p less than 0.0001), and have more left ventricular dysfunction (ejection fraction 0.60 +/- 14 versus 0.54 +/- 13, p less than 0.0001). To facilitate analysis and because of overlap between subgroups, we subdivided patients into three subgroups for statistical comparison of the years 1981 and 1987: subgroup I, no prior procedure (n = 1546 in 1981 and 1396 in 1987); subgroup II, optimal group (n = 503 in 1981 and 292 in 1987, and defined as no prior procedure, ejection fraction greater than or equal to 0.50 and age less than 65 years); subgroup III, patients having reoperations (n = 40 in 1981 and 117 in 1987). Internal mammary artery grafting was infrequently used in 1981 but was used in 72.1% in 1987. Major postoperative morbidity between the 2 years for the total population increased significantly: need for intraaortic balloon pumping, 1.4% versus 4.7%, p less than 0.0001; myocardial infarction 3.5% versus 5.5%, p less than 0.008; stroke, 1.4% versus 2.8%, p less than 0.008; and wound infection, 1.0% versus 3.0%, p less than 0.001. Wound infection (all types) in 1987 was increased sevenfold in patients having a perioperative myocardial infarction (0.7% versus 5%, p less than 0.0001). For young patients with good left ventricular function (subgroup II), there was no increase in these morbid events between 1981 and 1987. Hospital mortality in the total population increased significantly between 1981 and 1987 from 1.2% to 3.1% (p less than 0.0002), respectively. It was lowest for the patients in optimal condition (subgroup II) in both years, 0.8% versus 1.1%, and highest for reoperative patients, 5.3% versus 4.3%. In 1981, 58% of patients (503/870) were in the optimal group compared with 35% (292/828) in 1987 (p less than 0.0001). The last six years have seen a progressive trend in surgically treating older, sicker patients who have more complex disease, with a significant reduction in the best candidate group.(ABSTRACT TRUNCATED AT 400 WORDS)

Vasoactive drug effects on blood flow in internal mammary artery and saphenous vein grafts.

The internal mammary artery is a dynamic coronary graft, whereas the saphenous vein graft is passive. Therefore, potential exists not only for beneficial vasodilation but also for catastrophic spasm of the artery. The purpose of this study was to examine blood flow in the internal mammary and saphenous vein grafts during infusion of drugs that are commonly used after cardiac operations. A canine right heart bypass preparation allowed precise control of cardiac output, blood pressure, and heart rate, which were maintained constant during drug infusion. Both the internal mammary and saphenous vein grafts were constructed so that they perfused the same coronary bed: They were anastomosed in a Y fashion to a ligated anterior descending coronary artery. Electromagnetic flow probes measured graft flow (with the other graft occluded) before and after 15 minutes of drug infusion. The order of drug infusion was randomized and changes were compared by tests for paired differences. Phenylephrine (2 micrograms/kg/min) decreased flow in both the internal mammary and saphenous vein grafts, whereas norepinephrine (0.1 microgram/kg/min) increased flow in both grafts. Epinephrine (0.05 microgram/kg/min) increased mammary artery flow 16% +/- 6% but decreased saphenous vein graft flow 9% +/- 7%. Nitroglycerin (1 microgram/kg/min) significantly increased internal mammary flow (36% +/- 13%), from 47 +/- 7 to 59 +/- 7 ml/min (p less than 0.01), whereas flow decreased significantly in the saphenous vein graft 14% +/- 3%, from 64 +/- 9 to 59 +/- 8 ml/min (p less than 0.01). Nitroprusside (1 microgram/kg/min) decreased mammary artery flow 12% +/- 2%, from 50 +/- 7 to 44 +/- 7 ml/min (p less than 0.01), but increased saphenous vein graft flow 25% +/- 8%, from 64 +/- 9 to 77 +/- 7 ml/min (p less than 0.01). All hemodynamic variables were unchanged, except for norepinephrine, which significantly increased the first derivative of left ventricular pressure. The results suggest that flow through the canine internal mammary artery is changed by the drugs commonly used in perioperative management. Epinephrine and nitroglycerin increased internal mammary artery flow and decreased saphenous vein graft flow, whereas nitroprusside had the opposite effect. The vascular reactivity of the internal mammary artery must be considered when these drugs are used after coronary revascularization.