Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.

BACKGROUND: Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent. METHODS AND RESULTS: Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the beta-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the beta-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (P<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months. CONCLUSIONS: In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation beta-blocker.

A randomized trial of the low-molecular-weight heparin certoparin to prevent restenosis following coronary angioplasty.

OBJECTIVES: The objectives of this study were to evaluate the effectiveness and safety of the low-molecular-weight heparin (LMWH) certoparin in preventing restenosis following balloon coronary angioplasty. BACKGROUND: Restenosis following coronary angioplasty continues to limit the long-term efficacy of this procedure. Animal studies have indicated a potential role for LMWH in reducing restenosis by limiting smooth muscle proliferation. METHODS: This study tested the effects of certoparin, self-administered for 3 months, in reducing restenosis following balloon coronary angioplasty. One hundred and eighteen patients with 158 lesions treated with angioplasty were enrolled in this randomized, placebo-controlled trial. One hundred and two patients completed the study. The endpoint was relative loss measured with quantitative coronary angiography. RESULTS: The relative loss for placebo was 0.19 +/- 0.23 compared to 0.14 +/- 0.21 for LMWH (p = NS). The minimum lumen diameter (MLD) was 1.47 +/- 0.66 for placebo and 1.40 +/- 0.57 for the LMWH (p = NS). There was a reduction (31% for LMWH; 49% for placebo PSDP) in the percent of patients having binary restenosis (MLD < 50% of reference diameter). At the end of the study 77% of the placebo patients and 76% of the LMWH group were asymptomatic (p = NS). There was a low rate of bleeding complications and these were minor. Bone density scans showed that there was no significant occurrence of osteoporosis with 3 months of LMWH. CONCLUSIONS: Administration of certoparin for 3 months is safe, but appears ineffective in reducing post-PTCA restenosis.

"Stunning" of the left atrium after spontaneous conversion of atrial fibrillation to sinus rhythm: demonstration by transesophageal Doppler techniques in a canine model.

OBJECTIVES: This study compared left atrial and left atrial appendage contraction velocities in sinus rhythm before and after a brief period of atrial fibrillation in a canine model. BACKGROUND: In patients, left atrial appendage contraction velocities measured during sinus rhythm after cardioversion from atrial fibrillation are depressed relative to left atrial appendage emptying velocities measured during atrial fibrillation, suggesting that the left atrial appendage is mechanically "stunned." METHODS: This phenomenon was studied in a canine model of acute (60 min) pacing-induced atrial fibrillation followed by spontaneous reversion to sinus rhythm using epicardial and transesophageal pulsed wave Doppler. Unique features of the model include: 1) comparison of left atrial function postconversion to baseline sinus rhythm rather than to measurements during atrial fibrillation, 2) control of the duration of atrial fibrillation and 3) elimination of the extraneous influences of direct current shock and antiarrhythmic agents, which may independently depress left atrial function. RESULTS: Hemodynamic conditions (heart rate, mean arterial pressure, cardiac output, mean pulmonary artery pressure, mean right atrial pressure and mean left atrial pressure) at baseline, during 60 min of atrial fibrillation and after reversion to sinus rhythm were constant throughout the study period. Peak left atrial contraction velocities (measured from the transmitral flow velocity profile) were significantly (p < 0.02) reduced to 64+/-22% of baseline values upon spontaneous conversion of atrial fibrillation to sinus rhythm and recovered to basal values by 20 min after resumption of sinus rhythm. Peak left atrial appendage contraction velocities were significantly (p < 0.001) reduced to 49+/-24% of baseline values upon spontaneous conversion of atrial fibrillation to sinus rhythm and recovered to basal values by 40 min after reversion to sinus rhythm. CONCLUSIONS: Even brief (60 min) periods of atrial fibrillation in normal canine hearts result in marked depression of global left atrial systolic function and regional left atrial (left atrial appendage) systolic function upon resumption of sinus rhythm. This "mechanical stunning" of left atrial systolic function appears to be more profound and of longer duration for the left atrial appendage compared with the left atrium as a whole, which may predispose the appendage to blood stasis and thrombus formation. Chronic models of atrial fibrillation need to be developed to examine the impact of longer periods of atrial fibrillation upon the magnitude and duration of postconversion left atrial "stunning."

Assessment of outcome of bifurcation lesions and non-bifurcation lesions treated in the CAVEAT trial. CAVEAT investigator group.

Registry data suggests that bifurcation lesions are associated with reduced success during percutaneous revascularization. We studied 1012 CAVEAT patients to compare procedural outcomes in patients with and without bifurcation lesions whose target vessel was treated with either atherectomy or angioplasty. Bifurcation lesions have increased angiographic complexity and interventions on them are associated with lower acute procedural success rates compared to non-bifurcation lesions. Subgroup analysis suggests that atherectomy treatment of bifurcation lesions improves acute procedural success rates and lowers restenosis rates compared to angioplasty treatment of bifurcation lesions but atherectomy of bifurcation lesions is associated with higher acute complication rates than angioplasty of bifurcation lesions.

Effect of acute pericardial tamponade on the relative contributions of systolic and diastolic pulmonary venous return: a transesophageal pulsed Doppler study.

The effect of acute pericardial tamponade on pulmonary venous return was assessed by transesophageal pulsed Doppler echocardiography. In 14 open-chest anesthetized dogs peak pulmonary venous flow velocities in systole (VJ) and in diastole (VK) were measured during apnea and atrial pacing while acute tamponade was induced by intrapericardial instillation of 0.9% sodium chloride solution. Before intravascular volume expansion, induction of acute tamponade resulted in a significant decline in VK (43 +/- 17 to 19 +/- 8 cm/sec; p < 0.05) but no change in VJ or the ratio VJ/VK. After intravascular volume expansion, induction of acute tamponade resulted in significant reductions in VJ (43 +/- 9 to 29 +/- 10 cm/sec; p < 0.001) and VK (37 +/- 19 to 15 +/- 11 cm/sec; p < 0.001). The effect was disproportionately greater on VK, however, resulting in a significant increase in VJ/VK (1.51 +/- 0.84 to 2.58 +/- 1.41; p < 0.001). The disproportionate effect of acute tamponade on VK suggests that increased pericardial pressure directly constrains diastolic filling of the left atrium as a conduit to the left ventricle and that it does not decrease the systolic and diastolic phases of pulmonary venous return uniformly. Intravascular volume expansion increases cardiac output before acute tamponade, but during acute tamponade it amplifies the disproportionate impact of increased pericardial pressure on left ventricular diastolic filling as the left ventricle is constrained within the fluid-filled pericardial sac.

Effects of contrast media on coronary hemodynamics and myocardial metabolism.

RATIONALE AND OBJECTIVES: This study was designed to compare the effects of ionic contrast medium (CM), Renografin-76 (R76), and nonionic CM, Omnipaque-350 (OM350), on coronary hemodynamics and myocardial metabolism. METHODS: In 10 open-chest, atrial-paced dogs, 4 mL of R76 and OM350 were injected into the left anterior descending coronary artery. Coronary blood flow (CBF), myocardial oxygen consumption (MVO2), lactate extraction (LE), left ventricular (LV) dp/dt, and aortic systolic pressure (AOP) were measured. RESULTS: The maximal CBF changes caused by OM350 and R76 were 23.7 +/- 3.3 mL/minute and 18.3 +/- 3.3 mL/minute (NS), respectively. OM350 produced an increase in LV dp/dt by 378 +/- 85 mm Hg/second, which was different from -244 +/- 65 mm Hg/second by R76 (P < .05). The changes in MVO2 and LE after OM350 injection were 2.6 +/- 0.6 mL/minute and 10.2 +/- 5 microM/minute, respectively; those were different from -0.1 +/- 0.4 mL/minute, and -7.7 +/- 5.1 microM/minute after R76 injection (P < .05). CONCLUSION: Although both agents increased CBF, they appeared to act by different mechanisms. That a direct coronary vasodilator effect is the main action of R76 on coronary vascular response is suggested by decreasing myocardial contractility and oxygen consumption. However, OM350, by enhancing both parameters, may augment CBF at least in part by autoregulation.

Impairment of myocardial vascular responsiveness after transient myocardial ischemia and reperfusion.

Coronary vascular responses after brief periods of myocardial ischemia are impaired. Whereas some studies suggest that the ischemic insult selectively depresses endothelium-dependent vasodilator mechanisms, other studies indicate that even responses to direct vascular smooth-muscle relaxants such as adenosine may be decreased. This study was undertaken to measure regional myocardial blood flow (RMBF) responses to adenosine (a direct coronary vasodilator) and serotonin (an indirect, endothelium-dependent vasodilator) in myocardium subjected to regional ischemia followed by reperfusion. Temporary regional ischemia was achieved by 20 minutes of occlusion of the left anterior descending coronary artery (LAD) followed by 20 minutes of reflow in 10 open-chest anesthetized dogs. In the left circumflex coronary artery (LCX) territory, which served as a nonischemic control, RMBF (measured with radioactive microspheres) increased significantly in response to left atrial infusions of adenosine (1.29 +/- 0.27 to 3.89 +/- 3.89 +/- 2.15 ml/min/gm; p < 0.001) and serotonin (1.29 +/- 0.27 to 3.29 +/- 1.49 ml/min/gm; p < 0.001) and the percent reduction in coronary vascular resistance (% delta CVR) was comparable for these two pharmacologic probes (65% +/- 26% vs 62% +/- 19%; difference not significant [NS]). In contrast, in the myocardium supplied by the LAD, which was subjected to ischemia followed by reperfusion, the augmentation of RMBF by adenosine (1.07 +/- 0.29 to 1.82 +/- 1.35 ml/min/gm; p < 0.001) and serotonin (1.07 +/- 0.29 to 2.37 +/- 1.21 ml/min/gm; p < 0.001) was blunted.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis presented with unstable angina and myocardial infarction: one explanation for late cardiac events following directional coronary atherectomy.

Three cases of restenosis after directional coronary atherectomy (DCA) presented with unstable angina and then myocardial infarction. Two of them were complicated with malignant ventricular dysrhythmia. A total or subtotal thrombotic occlusion at the DCA site was shown. This fulminating course of restenosis could partially explain the higher late cardiac morbidity and mortality after DCA than after percutaneous transluminal balloon angioplasty.

Alterations in transmitral flow dynamics in patients with early mitral valve closure and aortic regurgitation.

Ten patients with severe aortic regurgitation (AR) and early diastolic mitral closure demonstrated by M-mode echocardiography (group I) were compared to 10 age-matched patients with severe AR and normal timing of mitral closure to quantify the accompanying alterations in transmitral flow dynamics assessed by pulsed Doppler echocardiography. Transmitral filling period expressed as a fraction of the time available for diastolic filling was significantly shortened in group I patients relative to group II patients (0.50 +/- 0.10 vs 1.04 +/- 0.09, p < 0.001) because early mitral closure truncated transmitral filling and obliterated the atrial contribution to left ventricular filling. The rapid diastolic filling period normalized for the time available for diastolic filling was also shortened for group I patients relative to group II patients (0.49 +/- 0.11 vs 0.64 +/- 0.19; p < 0.05). Early mitral closure in group I patients was functionally incomplete because 9 of the 10 patients had diastolic mitral regurgitation, which was not detected in any patients in group II (p < 0.001). Thus the group I patients with early mitral closure and severe aortic regurgitation had truncated transmitral inflow and diastolic mitral regurgitation. These patients had higher pulmonary capillary wedge pressures (32 +/- 6 vs 11 +/- 9 mm Hg; p < 0.001) and more severe functional limitation (p < 0.001) than group II patients.

Acute procedural results in the treatment of 30 coronary artery bifurcation lesions with a double-wire atherectomy technique for side-branch protection.

Percutaneous treatment of bifurcation lesions has been consistently shown to be associated with lower acute success rates, higher initial complication rates, and an increased rate of restenosis when compared with findings in nonbifurcation lesions. Recent analysis of data from a CAVEAT subgroup suggests that directional atherectomy of bifurcation lesions can improve initial success rates and lower restenosis rates but at the cost of high complication rates. Reports from several angioplasty series document improved success rates and lower complication rates with the use of a two-wire technique to protect side branches when treating bifurcation lesions. Our experience with a two-wire atherectomy technique that uses a nitinol wire to protect important side branches is presented.

The fracture, dislodgement and retrieval of a probe III balloon-on-a-wire catheter.

The fracture and dislodgement of an angioplasty device within the coronary arteries is a rare but increasingly noted complication. If the fragment of angioplasty balloon or guidewire is dislodged in a proximal and patent coronary artery, the likelihood of acute embolization which could lead to an acute coronary thrombus and/or myocardial infarction exists. Therefore, the immediate removal of the broken piece of the angioplasty catheter is imperative. A case of unusual fracture and dislodgement of a Probe III Balloon-on-A-Wire catheter and retrieval of the broken piece is reported.

Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. METHODS AND RESULTS: Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, his family, and/or hospital records. Hospitalization data also were obtained for patients who had died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission. In Vasodilator-Heart Failure Trial (V-HeFT) I, no significant difference in number of patients hospitalized or number of hospitalizations was noted among the treatment groups, although there was a trend for fewer and delayed cardiac hospitalizations in the hydralazine plus isosorbide dinitrate arm in which the survival was greater. In V-HeFT II, no difference in hospitalizations was apparent between the enalapril and hydralazine plus isosorbide dinitrate arms. Univariate predictors of hospitalization for all causes were reduced peak oxygen consumption (VO2) during exercise (p < 0.0001), reduced exercise duration (p < 0.0001), increased cardiothoracic ratio on chest radiograph (p < 0.0001), increased age (p < 0.03), and use of antiarrhythmic drugs (p < 0.013), whereas multivariate predictors were reduced peak VO2 (p < 0.0001), use of antiarrhythmic drugs (p < 0.015), and increased cardiothoracic ratio (p < 0.03). Univariate predictors of hospitalization for heart failure were peak VO2 (p < 0.0001), LVEF (p < 0.0001), reduced exercise duration (p < 0.0001), elevated cardiothoracic ratio (p < 0.0001), and elevated plasma norepinephrine (p < 0.0001). Multivariate predictors were exercise duration (p < 0.0001), LVEF (p < 0.04), elevated cardiothoracic ratio (p < 0.03), plasma norepinephrine (p < 0.0005), and coronary artery disease (p < 0.02). Time to first hospitalization, cause specific or overall, was considerably shorter for patients with baseline peak VO2 < 10 mL.kg-1 x min-1 compared with those with peak VO2 > 15 mL.kg-1 x min-1. CONCLUSIONS: Despite better survival in patients randomized to hydralazine plus isosorbide dinitrate compared with placebo and better survival in patients randomized to enalapril compared with hydralazine plus isosorbide dinitrate, no significant differences between the treatment groups were apparent in the incidence of hospitalization or time to first hospitalization for congestive heart failure, for cardiac reasons other than congestive heart failure, or for other causes. V-HeFT I and V-HeFT II data demonstrate no treatment effect on hospitalization, perhaps reflecting in part the effectiveness of the Veterans Affairs special heart failure clinics in dealing with worsening heart failure on an outpatient basis. Identification of predictors of hospitalization were similar in both studies.

Regional changes in blood flow, extracellular potassium and conduction during myocardial ischemia and reperfusion.

OBJECTIVES: We postulated that ventricular arrhythmias may arise from the heterogeneous washout of ischemic metabolites. Our objective was to investigate the distribution of extracellular potassium concentration ([K+]o) during myocardial ischemia and reperfusion and to correlate this distribution with regional differences in myocardial blood flow. BACKGROUND: Our previous study showed that reperfusion after a brief period of ischemia resulted in heterogeneous reflow of the ischemic myocardium. METHODS: The changes in regional myocardial blood flow, midmyocardial [K+]o and electrogram duration were quantitated in 14 dogs undergoing 20 min of left anterior descending coronary artery occlusion and 1 min of reperfusion. Regional myocardial blood flow was measured by using 15-microns radioactive microspheres in 1- to 1.5-g full thickness myocardial samples. The [K+]o was measured with intramyocardial K(+)-sensitive electrodes. RESULTS: During coronary occlusion, the ischemic zone exhibited a reduction in regional blood flow to 0.13 +/- 0.06 ml/g per min and increases in [K+]o to 9.3 +/- 2.6 mmol/liter and electrogram duration to 131.8 +/- 38.6% of control. Heterogeneous reduction in regional blood flow at various sites in the ischemic zone had fair correlations with variable increases in [K+]o (r = -0.70) and electrogram duration (r = -0.75). During min 1 of reperfusion, regional blood flow ranged from two to more than seven times baseline, resulting in a disorganized spatial distribution of perfusion with islands of high and low blood flows. Associated with the heterogeneous early reperfusion regional myocardial blood flow, [K+]o and electrogram duration changed at different rates toward normal. Whereas correlation between regional blood flow and [K+]o or standardized electrogram duration was fair during ischemia, this correlation was poor during early reperfusion. CONCLUSIONS: Spatial heterogeneity in regional myocardial blood flow during myocardial ischemia and early reperfusion is associated with heterogeneity in [K+]o and electrophysiologic characteristics, which in turn may play an important role in the genesis of arrhythmias arising from the ischemic and reperfused myocardium.

New approach to management of intraaortic balloon pumps in patients with peripheral vascular disease: case reports of four patients requiring urgent IABP insertion.

Four selected cases of emergent IABP insertion in PV patients are presented. After angiographic documentation of critical iliac stenosis, conservative peripheral angioplasty was performed prior to IABP insertion. No patient experienced a peripheral ischemic event associated with IABP use.

Effects of intracoronary administration of contrast media on myocardial high-energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol.

Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia.

Effects of intracoronary administration of contrast media on coronary hemodynamics in a canine post ischemic reperfusion model.

Hemodynamic changes due to intracoronary injections of nonionic contrast medium Omnipaque-350 (OM), ionic dimer Hexabrix (HB), and ionic contrast medium Renografin-76 (R76) were compared at baseline and during reperfusion after a 30-minute left anterior descending coronary artery (LAD) occlusion. In 11 open chest, anesthetized, and atrially paced dogs, 4 ml of either OM, HB, R76, or 0.9% NaCl were injected into the carotid-LAD bypass system. Coronary blood flow (CBF) and coronary vascular resistance (CVR) were measured before, during and after the intracoronary injection. The maximal hyperemic change (in percentage) from the preinjection value of CBF and CVR were calculated. The results at baseline and during reperfusion for CBF were: 104 +/- 14% vs. 85 +/- 10% for OM (NS); 76 +/- 11% vs. 39 +/- 9% for R76 (p less than 0.05); 57 +/- 8% vs. 33 +/- 5% for HB (P less than 0.05); and 30 +/- 7% vs. 9 +/- 4% for 0.9% NaCl (p less than 0.05). Consequently, the hyperemic changes of CVR at baseline and during reperfusion were: -49 +/- 3 vs. -42 +/- 4% for OM (NS); -44 +/- 3% vs. -24 +/- 6% for R76 (p less than 0.01); -36 +/- 3% vs. -24 +/- 4% for HB (p less than 0.05); and -18 +/- 4% vs. -7 +/- 3% for 0.9% NaCl (p less than 0.05). Thus, ischemia and reperfusion significantly dampened the coronary hemodynamic and vascular response to R76, HB, and 0.9% NaCl but not to OM. The preserved coronary vascular reserve with high flow in this canine post-ischemic reperfusion model may explain the advantage of nonionic over ionic contrast media used in emergency coronary angiography following thrombolysis.

The effect of sodium on hemodynamic changes during coronary angiography with nonionic contrast media.

To investigate the effect of sodium on cardiac hemodynamics, sodium chloride was added to nonionic contrast media to a 0.9% concentration and was compared with the standard media iohexol, iopamidol, and ioversol. Left coronary angiography was performed in 10 closed-chest, atrial-paced dogs with 10 ml injections of each preparation in a randomized and blinded fashion. The maximum changes in left ventricular systolic pressure, mean aortic pressure, left ventricular and diastolic pressure, and maximal rise of left ventricular pressure were measured. The left ventricular systolic pressure and mean aortic pressure decreased by 17 +/- 7 mm Hg and by 12 +/- 5 mm Hg with iohexol plus 0.9% NaCl, but only by 5 +/- 4 mm Hg and by 4 +/- 3 mm Hg with iohexol alone (p less than 0.001). The left ventricular and end diastolic pressure increased by 2.2 +/- 0.6 mm Hg with iohexol plus 0.9% NaCl, but did not change with iohexol alone (p less than 0.001). Left ventricular dp/dt decreased by 204 +/- 161 mm Hg/sec with iohexol plus 0.9% NaCl but increased by 392 +/- 122 mm Hg/sec with iohexol alone (p less than 0.001). Similar results were obtained from experiments with iopamidol versus iopamidol plus 0.9% NaCl and ioversol versus ioversol plus 0.9% NaCl. Ioversol plus 5% dextrose or ioversol plus 2.1% choline chloride (isomolar to ioversol plus 0.9% NaCl) produced a significant increase in left ventricular systolic pressure and left ventricular dp/dt (versus ioversol plus 0.9% NaCl, p less than 0.001). Thus, sodium, but not the osmolality or chloride, contributed to the negative inotropic effect of the contrast media.(ABSTRACT TRUNCATED AT 250 WORDS)

Progression of native coronary artery disease at 10 years: insights from a randomized study of medical versus surgical therapy for angina.

Repeat coronary angiography was performed in 42 patients 10 years after randomization to medical (n = 21) or surgical (n = 21) therapy for chronic angina. The native coronary arteries were classified into 15 angiographic segments and 3 arterial trunks for analysis of progression of coronary artery disease. The incidence rate of disease progression in coronary segments was 24% and 28% in medically and surgically treated patients, respectively (p = NS). Grafted segments showed a 38% rate of disease progression, which was higher than the 18% rate of for nongrafted segments (p less than 0.001) and the overall rate of 24% for medically treated patients (p less than 0.01). Similarly, 29 (94%) of 31 grafted arteries exhibited disease progression compared with 19 (59%) of 32 nongrafted arteries (p less than 0.01) and 42 (67%) of 63 arteries in medically treated patients (p less than 0.01). In grafted vessels, disease progression occurred more often in arteries proximal (84%) to the anastomosis than in arteries distal (16%) to graft insertion (p less than 0.001). Progression occurred in 46% of proximal segments compared with 23% of distal segments (p less than 0.02). Progression was seen in 23 (55%) of 43 segments with an occluded graft compared with 30 (31%) of 96 segments with a patent graft (p less than 0.02). Ten years after randomization, medically and surgically treated patients showed a comparable rate of disease progression in coronary segments. However, surgical therapy appeared to significantly accelerate atherosclerotic progression in the grafted vessels, especially in the proximal portions. Occluded grafts also correlated with an adverse effect on disease progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of cyclosporine in the mouse heterotopic heart transplant model.

We refined the mouse ear-heart transplant model developed by Fulmer and coworkers and tested cyclosporine as a sole immunosuppressive agent in this model. Three-week-old CBA mice were used as heart recipients, and unsexed newborn BALB/c mice were used as heart donors. The heart grafts were examined for visible pulsations at 10-fold to 20-fold magnification daily for the first 10 days and every other day thereafter. Graft electrocardiograms were also obtained on the same schedule. Preliminary studies had established that a dose of 15 mg/kg/day was the optimal cyclosporine dose in our model. This dose was administered subcutaneously to each of two treatment groups. Group 2 received this dose for the entire 30-day experimental period. Group 3 received this dose for the first 16 days of the experimental period. Group 1 consisted of allografts receiving no immunosuppression. Group 1 grafts showed evidence of initial successful engraftment by day 7; however, by day 13 none of the grafts remained viable. In group 2, 19 of 23 grafts remained viable for the entire experimental period. In group 3, all of the grafts remained viable until day 17 (after day 16 cyclosporine was discontinued) and rapidly lost evidence of viability thereafter. By day 21, none of the grafts in group 3 remained viable. Survival curves for the three groups as determined by electrocardiogram and visible pulsations were constructed, and the differences between the curves were significant (p = 0.001). The results of this study demonstrate the potential usefulness of the ear-heart transplantation model in screening immunosuppressive agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ionic and nonionic contrast media on bradyarrhythmia during coronary angiography: a comparison of Renografin-76, Hypaque-76, and Isovue-370.

Contrast media occasionally produce bradyarrhythmias defined as a 25% decrease in heart rate and/or developing atrioventricular block during coronary angiography. Twelve left coronary angiographies and seven right coronary angiographies were performed with 10 ml of diatrizoate meglumine and diatrizoate sodium (Renografin-76 [R76] or Hypaque [H76]) or iopamidol (Isovue 370 [ISO]) in a blinded randomized fashion. Heart rate decreased significantly from 135 +/- 5 to 120 +/- 5 beats/min (p less than 0.001) with R76, to 127 +/- 7 beats/min (p less than 0.01) with H76, and to 130 +/- 6 beats/min (p less than 0.05) with ISO in left coronary angiographies; more profound decrease was observed in right coronary angiographies from 134 +/- 4 to 87 +/- 18 beats/min (p less than 0.001) with R76, to 99 +/- 14 beats/min (p less than 0.001) with H76, and to 125 +/- 7 beats/min (p less than 0.01) with ISO. In 12 left coronary angiographies bradyarrhythmia was observed in five cases with R76, two with H76, and none with ISO. In seven right coronary angiographies it occurred in six with R76, three with H76, and none with ISO. The differences in the incidence of bradyarrhythmia between R76 and ISO were significant during left and right coronary angiographies (p less than 0.05 and p less than 0.01, respectively). Thus ionic contrast media produced more marked bradyarrhythmias than nonionic contrast media in coronary angiography, especially R76. Right coronary angiography resulted in more profound bradyarrhythmias than left coronary angiographies. This study suggested that nonionic contrast media (ISO) might be preferable to ionic contrast media (R76 or H76) for coronary arteriography.