Assessment of the efficacy of interventions to limit ischemic injury by direct measurement of intramural carbon dioxide tension after coronary artery occlusion in the dog.

Although numerous interventions have been shown to exert a salutary effect on the ischemic myocardium, the severity of ischemia generally has been measured by indirect techniques. In the present investigation the effect of ischemia on intramural carbon dioxide tension (PmCO(2)) was measured directly in the open-chest, anesthetized dog with a mass spectrometer during repetitive 10-min coronary artery occlusions separated by 45-min periods of reflow; simultaneously, regional myocardial blood flow in the ischemic area was measured by (127)Xenon washout. In all dogs the increase in PmCO(2) from before to 10 min after the first occlusion (DeltaPmCO(2)) exceeded that during subsequent occlusions. In those dogs not receiving an intervention (controls), DeltaPmCO(2) during the third occlusion was similar to that during the second occlusion. When propranolol, hyaluronidase, and nitroglycerin were administered to different groups of dogs before the third occlusion, each caused significantly smaller elevations in DeltaPmCO(2) than those occurring during the control second occlusion, and the combination of all three interventions induced the smallest increase in DeltaPmCO(2). Regional myocardial blood flow rose with hyaluronidase and was unchanged with propranolol, nitroglycerin, and the three drugs in combination. In contrast to these beneficial interventions, isoproterenol infused with the third occlusion caused a higher DeltaPmCO(2) than during the control second occlusion. It is concluded, first, that interventions that modify the severity of ischemia can be evaluated by measuring intramural carbon dioxide tension; second, that propranolol, hyaluronidase, and nitroglycerin reduce ischemic injury, whereas isoproterenol increases it; and third, that the combination of propranolol, hyaluronidase, and nitroglycerin exerts an additive beneficial effect on ischemia.

Effects of intranasal cocaine on sympathetic nerve discharge in humans.

Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these excitatory and inhibitory neural influences determines the net effect of cocaine on sympathetic discharge targeted to the human skeletal muscle circulation.

Assessment of coronary arterial restenosis with phase-contrast magnetic resonance imaging measurements of coronary flow reserve.

BACKGROUND: After successful percutaneous coronary arterial revascularization, 25% to 60% of subjects have restenosis, a recurrent coronary arterial narrowing at the site of the intervention. At present, restenosis is usually detected invasively with contrast coronary angiography. This study was performed to determine if phase-contrast MRI (PC-MRI) could be used to detect restenosis noninvasively in patients with recurrent chest pain after percutaneous revascularization. METHODS AND RESULTS: Seventeen patients (15 men, 2 women, age 36 to 77 years) with recurrent chest pain >3 months after successful percutaneous intervention underwent PC-MRI measurements of coronary artery flow reserve followed by assessments of stenosis severity with computer-assisted quantitative coronary angiography. The intervention was performed in the left anterior descending coronary artery in 15 patients, one of its diagonal branches in 2 patients, and the right coronary artery in 1 patient. A PC-MRI coronary flow reserve value /=70% and >/=50%, respectively. CONCLUSIONS: Assessments of coronary flow reserve with PC-MRI can be used to identify flow-limiting stenoses (luminal diameter narrowings >70%) in patients with recurrent chest pain in the months after a successful percutaneous intervention.

Visualization and functional assessment of proximal and middle left anterior descending coronary stenoses in humans with magnetic resonance imaging.

BACKGROUND: Coronary artery bypass grafting improves survival in patients with >70% luminal diameter narrowing of the 3 major epicardial coronary arteries, particularly if there is involvement of the proximal portion of the left anterior descending (LAD) coronary artery. Measurement of coronary flow reserve can be used to identify functionally important luminal narrowing of the LAD artery. Although magnetic resonance imaging (MRI) has been used to visualize coronary arteries and to measure flow reserve noninvasively, the utility of MRI for detecting significant LAD stenoses is unknown. METHODS AND RESULTS: Thirty subjects (23 men, 7 women, age 36 to 77 years) underwent MRI visualization of the left main and LAD coronary arteries as well as measurement of flow in the proximal, middle, or distal LAD both at rest and after intravenous adenosine (140 microgram/kg per minute). Immediately thereafter, contrast coronary angiography and when feasible, intracoronary Doppler assessments of coronary flow reserve, were performed. There was a statistically significant correlation between MRI assessments of coronary flow reserve and (a) assessments of coronary arterial stenosis severity by quantitative coronary angiography and (b) invasive measurements of coronary flow reserve (P<0.0001 for both). In comparison to computer-assisted quantitative coronary angiography, the sensitivity and specificity of MRI for identifying a stenosis >70% in the distal left main or proximal/middle LAD arteries was 100% and 83%, respectively. CONCLUSIONS: Noninvasive MRI measures of coronary flow reserve correlated well with similar measures obtained with the use of intracoronary Doppler flow wires and predicted significant coronary stenoses (>70%) with a high degree of sensitivity and specificity. MRI-based measurement of coronary flow reserve may prove useful for identification of patients likely to obtain a survival benefit from coronary artery bypass grafting.

Risk stratification before thrombolytic therapy in patients with acute myocardial infarction. The Thrombolysis in Myocardial Infarction (TIMI) Phase II Co-Investigators.

Several studies in the prethrombolytic era on the treatment of acute myocardial infarction identified selected variables from the patient's history, physical examination, chest roentgenogram and electrocardiogram that could be used to estimate mortality in patients with evolving infarction. To extend such assessment to patients receiving thrombolytic therapy, this study evaluated the prognostic utility of several risk factors in the 3,339 patients (2,742 men, 597 women, aged 24 to 78 years) enrolled in Phase II of the Thrombolysis in Myocardial Infarction (TIMI) trial. Before intravenous tissue plasminogen activator was given, the presence of each of eight risk factors was noted: age greater than or equal to 70 years, female gender, a history of diabetes mellitus or previous myocardial infarction, electrocardiographic evidence of evolving anterior infarction or atrial fibrillation, evidence on physical examination of mild pulmonary congestion or hypotension (systolic pressure less than 100 mm Hg) and sinus tachycardia (heart rate greater than 100 beats/min). Of the 3,339 patients, the 78 with pulmonary edema or cardiogenic shock were excluded because their risk was known to be high. Of the remaining 3,261, 864 (26%) had no risk factor (low risk); their mortality rate at 6 weeks was only 1.5%. In contrast, 2,397 (74%) had one or more risk factors (not low risk); of these, 5.3% died in 6 weeks (p less than 0.001). Among those with one or more risk factors, mortality at 6 weeks was related to the number of risk factors on admission; those with four or more had a mortality rate at 6 weeks of 17.2%. Thus, these eight risk factors can be easily remembered and assessed in patients with myocardial infarction who are candidates for thrombolytic therapy and can be used to estimate short-term mortality.

Prognosis after valve replacement in patients with severe aortic stenosis and a low transvalvular pressure gradient.

OBJECTIVES: This study was conducted to determine the risks and benefits of valve replacement in patients with severe aortic stenosis and a low transvalvular pressure gradient. BACKGROUND: There is uncertainty regarding the appropriate management of adults with severe aortic stenosis and a transvalvular pressure gradient < or = 30 mm Hg. With only six such patients reported, one study suggested that these subjects have a prohibitive operative risk and little symptomatic improvement if they survive surgical treatment, whereas another showed that they can survive an operation and improve symptomatically. METHODS: In an attempt to clarify the risks and benefits of valve replacement in these patients, we reviewed the records of 18 patients (15 men and 3 women, aged 49 to 81 years) with severe aortic stenosis (valve area < or = 0.4 cm2/m2 body surface area), a mean transvalvular pressure gradient < or = 30 mm Hg and limiting symptoms (New York Heart Association functional class III or IV) who underwent valve replacement. RESULTS: Six patients (33%) (95% confidence interval 13% to 59%) died perioperatively, whereas 10 patients (56%) (95% confidence interval 31% to 78%) improved symptomatically to functional class I (n = 8) or II (n = 2) (p = NS in comparison with the 6 who died). No clinical or hemodynamic variable was predictive of survival or improvement in functional class. CONCLUSIONS: Valve replacement in patients with severe aortic stenosis and a transvalvular pressure gradient < or = 30 mm Hg is accompanied by a considerable operative risk. Although there were no significant differences in this small series between the fraction of patients who died and those who exhibited improvement, we still recommend the procedure because many patients survive the operation and most of the survivors show an improved symptomatic status.

Effect of cocaine on coronary artery dimensions in atherosclerotic coronary artery disease: enhanced vasoconstriction at sites of significant stenoses.

Cocaine increases myocardial oxygen demand and paradoxically decreases oxygen supply by reducing coronary blood flow. Such "inappropriate" vasoconstriction also occurs with exercise, which causes intense vasoconstriction of coronary artery segments narrowed by atherosclerosis. This study was done to assess the cocaine-induced change in vasomotor tone of diseased and nondiseased coronary artery segments. In 18 patients (15 men, 3 women, aged 35 to 67 years), coronary artery areas in diseased and nondiseased segments were quantitated before and 15 min after administration of intranasal saline solution (6 patients) or cocaine (2 mg/kg body weight) (12 patients). No variables changed after intake of the saline solution. In response to cocaine, the luminal areas of diseased and nondiseased segments decreased, but the magnitude of vasoconstriction was greater in the diseased segments (mean +/- SD 29 +/- 23% versus 13 +/- 8%, p less than 0.05). Thus, cocaine causes vasoconstriction of diseased and nondiseased coronary artery segments, but its effect is particularly marked in the former.

Use of pulmonary capillary wedge pressure to assess severity of mitral stenosis: is true left atrial pressure needed in this condition?

There is disagreement concerning the use of the pulmonary capillary wedge pressure (in place of left atrial pressure) in assessing the presence and severity of mitral valve disease. This study was done to assess the accuracy and reliability of an oximetrically confirmed pulmonary capillary wedge pressure in measuring the transvalvular pressure gradient and valve area in patients with mitral stenosis. In 10 patients with mitral stenosis (1 man and 9 women; mean age +/- SD 47 +/- 7 years), pulmonary capillary wedge pressure was measured through an 8F Goodale-Lubin catheter with its wedge position confirmed by oximetry (oxygen saturation greater than or equal to 95%). In addition, a transseptal left atrial pressure was measured through a Brockenbrough catheter and left ventricular pressure was measured through a pigtail catheter. The mean and phasic left atrial and pulmonary capillary wedge pressures were similar (mean left atrial pressure 18 +/- 6 mm Hg; mean pulmonary capillary wedge pressure 18 +/- 8 mm Hg; p = NS). When the pulmonary capillary wedge pressure was used without adjustment for time delay, the transvalvular pressure gradient (9.8 +/- 3.3 mm Hg) and valve area (1.5 +/- 0.5 cm2) were significantly different (p less than 0.05) from the values obtained with use of left atrial pressure (7.2 +/- 2.9 mm Hg and 1.7 +/- 0.6 cm2, respectively). In contrast, when the pulmonary capillary wedge pressure was adjusted for the time delay through the pulmonary vasculature, the difference in gradients averaged only 1.7 mm Hg and the mitral valve areas were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleviation of cocaine-induced coronary vasoconstriction by nitroglycerin.

Cocaine induces vasoconstriction of epicardial coronary arteries in patients with and without coronary artery disease, and this vasoconstriction is particularly marked in segments narrowed by atherosclerosis. To assess the effect of nitroglycerin on cocaine-induced coronary vasoconstriction, computer-assisted quantitative analysis was performed on non-diseased and diseased coronary artery segments in 23 patients (18 men, 5 women, aged 43 to 65 years) 1) at baseline, 2) after administration of intranasal saline solution (in 8 patients) or 2 mg/kg of cocaine (in 15 patients), and then 3) after administration of sublingual placebo (in 6 patients) or 0.4 or 0.8 mg of nitroglycerin (in 9 patients) in the 15 patients given cocaine. In response to cocaine administration, coronary artery cross-sectional area decreased 22 +/- 7% (mean +/- SD) in non-diseased segments (p less than 0.05) and 45 +/- 18% in diseased segments (p less than 0.02). The magnitude of vasoconstriction was greater (p = 0.01) in the diseased segments. Sublingual nitroglycerin abolished the vasoconstriction in both non-diseased and diseased segments. Thus, nitroglycerin alleviates cocaine-induced vasoconstriction in patients with coronary artery disease.

Use of the left ventricular peak systolic pressure/end-systolic volume ratio to predict symptomatic improvement with valve replacement in patients with aortic regurgitation and enlarged end-systolic volume.

OBJECTIVES: This study was designed to assess the left ventricular peak systolic pressure/end-systolic volume (PSP/ESV) ratio in predicting symptomatic improvement with valve replacement in patients with aortic regurgitation and enlarged left ventricular volume. BACKGROUND: Patients with aortic regurgitation and a left ventricular end-systolic volume < or = 60 ml/m2 show symptomatic improvement with valve replacement, whereas the response of those with an enlarged end-systolic volume > 60 ml/m2 is mixed. Most benefit, but some do not. Valve replacement appears to help those whose end-systolic volume is enlarged because of excessive left ventricular afterload but appears to have little or no effect in those whose end-systolic volume is enlarged because of depressed left ventricular contractility. METHODS: We studied 27 patients (21 men and 6 women aged 18 to 72 years) with moderate or severe aortic regurgitation, no other cardiovascular abnormalities and left ventricular end-systolic volume > 60 ml/m2. In this group we assessed the ability of preoperative variables routinely measured at cardiac catheterization to predict symptomatic improvement with valve replacement. RESULTS: Of the 27 subjects, 1 (4%) died 51 days postoperatively. Six months postoperatively, symptoms had lessened in 17 patients (63%), were unchanged in 8 (29%) and had worsened in 1 (4%). By multivariate analysis, the PSP/ESV ratio was the strongest predictor of both functional class 6 months postoperatively (p = 0.026) and change in functional class from before operation to 6 months postoperatively (p = 0.033). By 6 months after valve replacement, all patients with a ratio > or = 1.72 mm Hg/ml per m2 were in functional class I or II; in contrast, of those with a ratio < 1.72 mm Hg/ml per m2, 31% were in functional class III, and 1 (8%) had died. CONCLUSIONS: The PSP/ESV ratio may help to predict which patients with aortic regurgitation and enlarged left ventricular end-systolic volume will have symptomatic improvement with valve replacement.

Acute systemic and coronary hemodynamic and serologic responses to cigarette smoking in long-term smokers with atherosclerotic coronary artery disease.

Previous studies suggested that cigarette smoking 1) inhibits an increase in coronary blood flow that should occur with increased myocardial oxygen demands, and 2) alters thromboxane and prostacyclin production, causing vasoconstriction and platelet aggregation. In 38 smokers (26 men and 12 women, aged 50 +/- 8 years [mean +/- standard deviation] ) with coronary artery disease, systemic and coronary hemodynamic and serologic variables were measured before and after smoking two cigarettes (in 8 to 10 minutes) (21 patients) or 8 to 10 minutes without smoking (17 patients; control group). No variable changed in the control group. Smoking increased (p less than 0.05) heart rate-systolic pressure product, cardiac output and maximal first derivative of left ventricular pressure (dP/dt) without significantly changing the coronary sinus concentrations of thromboxane B2 or 6-keto-prostaglandin F1 alpha (the stable metabolites of thromboxane A2 and prostacyclin, respectively). Smoking did not increase coronary flow in 6 of 11 patients with greater than 70% stenosis of the proximal left anterior descending or circumflex coronary artery, or both, whereas it caused an increase in coronary flow in all 10 patients without proximal stenoses (p = 0.006). To determine if smoking altered the response of coronary flow to increased myocardial oxygen demands, 10 smokers (5 men and 5 women, aged 48 +/- 9 years) underwent atrial pacing for 5 minutes followed 15 minutes later by atrial pacing for 5 minutes during smoking. In the five patients without proximal left coronary artery stenoses, coronary flow increased 26 +/- 29 ml/min with pacing and 45 +/- 21 ml/min with pacing/smoking (p = 0.018).(ABSTRACT TRUNCATED AT 250 WORDS)

Does indomethacin attenuate the coronary vasodilatory effect of nitroglycerin?

Although previous studies have shown that indomethacin attenuates the dilative effects of nitroglycerin on human peripheral veins and canine coronary arteries, its ability to alter the influence of nitroglycerin on coronary blood flow in human beings is unknown. In 22 patients (16 men and 6 women, aged 47 +/- 10 years [mean +/- standard deviation]) referred for the evaluation of chest pain, heart rate, systemic arterial pressure, coronary sinus blood flow (by thermodilution) and coronary vascular resistance (mean arterial pressure/coronary sinus blood flow) were measured before and during the administration of intracoronary saline solution (n = 6, [control subjects]) or intracoronary nitroglycerin, 100 micrograms (n = 16). Of these 16 patients, 8 had no pretreatment and the other 8 received 50 mg of indomethacin orally, 10 and 2 to 3 hours before study. In the six control subjects, no variable changed with saline injection. In the eight patients given nitroglycerin without indomethacin pretreatment, heart rate and mean systemic arterial pressure were changed modestly (72 +/- 15 to 74 +/- 15 beats/min and 93 +/- 9 to 87 +/- 13 mm Hg, respectively, p less than 0.05), coronary sinus blood flow increased by 56 +/- 43% (107 +/- 72 to 155 +/- 78 ml/min, p less than 0.001) and coronary vascular resistance decreased (1.12 +/- 0.50 to 0.66 +/- 0.26 mm Hg/ml per min, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

The use of tissue-type plasminogen activator for acute myocardial infarction in the elderly: results from thrombolysis in myocardial infarction Phase I, open label studies and the Thrombolysis in Myocardial Infarction Phase II pilot study. The TIMI Investigators.

The impact of age on hospital mortality, incidence of major hemorrhagic events and transfusion requirements was examined in 756 patients with acute myocardial infarction enrolled in the Thrombolysis in Myocardial Infarction (TIMI) Phase I, open label studies and the TIMI Phase II pilot study. The mortality rate significantly increased with age and was 3.5%, 11.5% and 12% in patients less than 65, 65 to 69 and 70 to 76 years of age, respectively (p less than 0.001). Logistic regression analyses selected female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, continuing chest pain immediately after recombinant tissue-type plasminogen activator (rt-PA) administration, low systolic blood pressure at the time of admission and advanced age as variables predictive of in-hospital death. The incidence of major hemorrhagic events among patients not undergoing cardiac surgery during hospitalization was 8.7%, 14.5% and 24.7% in patients aged less than 65, 65 to 69 and greater than or equal to 70 years, respectively (p less than 0.001). The majority of hemorrhages were secondary to cardiac catheterization or puncture wounds. Variables related to a major hemorrhagic event included protocol, age, rt-PA dose/kg body weight and elevated diastolic blood pressure on admission. Of five intracranial bleeding events, three occurred in patients greater than 65 years. Transfusion requirements significantly increased with age (p less than 0.001). Reperfusion status at 90 min in the TIMI Phase I and open label studies A to C was similar in the three age groups studied and ranged from 60% to 71%.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of intranasal cocaine in humans.

Intranasal cocaine, 2 to 3 mg/kg body weight, is a commonly used local anesthetic for rhinolaryngologic procedures, and many persons who abuse it ingest a similar amount. Previous studies in humans showed that this dose of cocaine causes coronary vasoconstriction, and studies in animals showed that larger amounts given intravenously diminish myocardial performance. This study assessed the hemodynamic effects of intranasal cocaine, 2 mg/kg, in humans. In 15 patients (8 men and 7 women, aged 30 to 70 years) referred for cardiac catheterization, heart rate, systemic arterial pressure, cardiac index, pulmonary capillary wedge and pulmonary artery pressures and left ventricular pressure and its first derivative (dP/dt) were measured before and 15, 30 and 45 min after intranasal administration of saline solution (n = 5) or cocaine, 2 mg/kg (n = 10). No variable changed with saline solution. In those given cocaine, there was an increase in heart rate (17 +/- 16%, mean +/- SD), mean systemic arterial pressure (8 +/- 7%), cardiac index (18 +/- 18%) and positive and negative dP/dt (18 +/- 20% and 15 +/- 22%, respectively) (p less than 0.05 for all). Thus, intranasal cocaine in a dose similar to that used medicinally or "recreationally" does not exert a deleterious influence on intracardiac pressures and left ventricular performance.

High dose intravenous streptokinase for acute myocardial infarction: preliminary results of a multicenter trial.

To assess the efficacy of intravenous streptokinase in patients with acute myocardial infarction, 40 patients (30 men and 10 women, mean age 54 years) with acute myocardial infarction were given 1.5 million U of streptokinase intravenously in 1 hour, and coronary arteriography was performed repeatedly to assess reperfusion. Streptokinase treatment was begun 270 +/- 86 (mean +/- SD) minutes after the onset of chest pain. Of the 40 patients, 34 had total or near total coronary occlusion before streptokinase administration. In 14 (41%) of these 34 patients, some reperfusion occurred during the 90 minutes after the administration of streptokinase, but in only 11 of the 14 was reperfusion present at 90 minutes. After streptokinase administration, all patients received heparin for 8 to 10 days; they were subsequently administered aspirin and dipyridamole. Clinical evidence of reocclusion during the first 24 hours of heparin therapy occurred in one patient. Thus, when given to patients with acute myocardial infarction and total coronary occlusion an average of 4 1/2 hours after the onset of chest pain, high dose intravenous streptokinase achieves reperfusion in only about 40% and results in sustained reperfusion in only about 30%.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND: Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS: We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS: Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS: There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting.

Noncardiac surgery in patients with coronary artery disease. Risks, precautions, and perioperative management.

Patients with coronary artery disease face increased risks when they undergo noncardiac surgery. This is attributable to the cardiovascular stress imposed by the surgical procedure and the effects of anesthetic agents on the cardiovascular system. Several approaches to managing patients with coronary artery disease before, during, and after noncardiac surgery include "prophylactic" myocardial revascularization procedures, digitalization, use of propranolol hydrochloride, and insertion of temporary intravenous pacemakers.

Abrupt change from propranolol to verapamil. Safety and feasibility in stable angina pectoris.

To study the safety and feasibility of abruptly changing antianginal therapy from propranolol hydrochloride to verapamil, we gave propranolol to ten patients with stable angina and coronary artery disease for 14 days, then, on day 15, we began verapamil therapy, which continued for 14 more days. Anginal frequency and nitroglycerin use were similar throughout the study. No patient had symptomatic bradycardia or atrioventricular block. Such crossover therapy is effective when propranolol is replaced by verapamil abruptly.

Utility of various radionuclide techniques for distinguishing ischemic from nonischemic dilated cardiomyopathy.

BACKGROUND: Clinically, ischemic and nonischemic (idiopathic) dilated cardiomyopathy may be difficult to distinguish. Radionuclide ventriculography and exercise testing with thallium-201 scintigraphy are often used in an attempt to differentiate them noninvasively. With these techniques, the presence of (1) left ventricular (LV) regional asynergy, (2) depressed LV systolic function with normal right ventricular function, and/or (3) thallium-201 perfusion abnormalities traditionally has been regarded as evidence of ischemic heart disease. We assessed the incidence with which these abnormalities occur in patients with nonischemic-dilated cardiomyopathy. METHODS: Seventy-six patients (45 men, 31 women, aged 18 to 75 years) with invasively proven nonischemic-dilated cardiomyopathy underwent radionuclide ventriculography (n = 75) and provocative thallium-201 perfusion imaging (n = 17). RESULTS: Regional LV wall motion abnormalities were noted in 48% of patients, and 54% had LV systolic dysfunction without concomitant right ventricular dysfunction. Reversible and/or fixed exercise-induced thallium-201 perfusion abnormalities occurred in 94% of the patients studied. CONCLUSIONS: Radionuclide ventriculography and exercise testing with thallium perfusion imaging cannot be used reliably to differentiate ischemic from nonischemic dilated cardiomyopathy, since many patients with the latter have radionuclide evidence of LV segmental wall motion abnormalities, selective LV systolic dysfunction, and segmental perfusion abnormalities.

Influence of cocaine, ethanol, or their combination on epicardial coronary arterial dimensions in humans.

BACKGROUND: Cocaine and ethanol are often abused concomitantly, and this combination may be more lethal than either substance alone. Although previous studies showed that cocaine causes coronary arterial vasoconstriction, the combined effect of cocaine and ethanol on the coronary vasculature in humans is unknown. Thus, we assessed the effects of intranasal cocaine, intravenous ethanol, or a cocaine-ethanol combination on heart rate, systemic arterial pressure, and coronary arterial dimensions in humans. METHODS: Thirty-four subjects with chest pain (27 men and seven women, aged 34 to 67 years) who were referred for catheterization received one of the following pharmacologic interventions: (1) intranasal (2 mL) and intravenous (5 mL/kg) saline (n = 8 [group A]); (2) intranasal cocaine (2 mg/kg) and intravenous saline (5 mL/kg) (n = 9 [group B]); (3) intranasal saline (2 mL) and intravenous 10% ethanol (5 mL/kg) (n = 9 [group C]); or (4) intranasal cocaine (2 mg/kg) and intravenous 10% ethanol (5 mL/kg) (n = 8 [group D]). Heart rate, systemic arterial pressure, left coronary arterial dimensions (by computer-assisted quantitative angiography), as well as blood cocaine, ethanol, and cocaine metabolite concentrations were measured before and 30, 60, and 90 minutes after initiation of the intravenous infusions. RESULTS: No hemodynamic or angiographic changes were observed in the group A (saline) subjects. In the group B (cocaine) subjects, the heart rate-systolic arterial pressure product increased by 5% and 10% at 30 and 90 minutes, respectively, and coronary arterial diameter decreased by 14% at these times. In the group C (ethanol) subjects, no hemodynamic changes were noted, but coronary arterial diameters increased by 12%, 11%, and 12% at 30, 60, and 90 minutes, respectively. In the group D (cocaine-ethanol) patients, rate-pressure product increased by 17%, 10%, and 16%, and coronary arterial diameters increased by 7%, 12%, and 13%, at 30, 60, and 90 minutes, respectively. CONCLUSION: The combination of intranasal cocaine and intravenous ethanol causes an increase in the determinants of myocardial oxygen demand. However, it also causes a concomitant increase in epicardial coronary arterial diameter.