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.

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.

Coronary angioplasty in the patient with acute myocardial infarction.

In patients with acute myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA) may be used (1) to restore antegrade flow in the infarct artery (so called "primary" PTCA) instead of thrombolytic therapy, (2) to establish antegrade coronary flow after unsuccessful thrombolytic therapy (so called "rescue" or "salvage" PTCA), and (3) to reduce the residual infarct artery stenosis after successful thrombolysis. This review examines the prospective, randomized studies that have addressed the use of PTCA for each of these purposes. In selected circumstances, PTCA is a reasonable alternative to thrombolytic therapy in patients with evolving or recent Q-wave myocardial infarction. In those patients with acute myocardial infarction complicated by cardiogenic shock, PTCA may be the preferred treatment. After thrombolytic therapy, the use of PTCA in the absence of spontaneous or provocable ischemia offers no benefit with regard to left ventricular function or survival. In this circumstance, its use is associated with an excessive risk of bleeding, transfusions, and emergent coronary artery bypass surgery when performed within hours of infarction.

Genetic modification of the vessel wall. Comparison of surgical and catheter-based techniques for delivery of recombinant adenovirus.

BACKGROUND: Gene transfer can potentially alter vessel wall biology and intervene in the pathogenesis of human disease. Although several methods for vector delivery have been described, systematic comparisons of these methods are unavailable. Therefore, this study compared three catheter-based strategies and a surgical technique to assess efficient and selective gene transfer to the vascular wall. METHODS AND RESULTS: The common carotid arteries and internal jugular veins of New Zealand White rabbits were infected with recombinant adenovirus encoding either firefly luciferase or a nuclear-localizing variant of beta-galactosidase. Delivery of recombinant virus was achieved by one of four methods: (1) instillation within a surgically isolated vessel segment (dwell), (2) a double-balloon catheter, (3) a perforated balloon catheter (Wolinsky), or (4) an angioplasty balloon catheter coated with a hydrophilic adsorbent polymer (Hydrogel). Vessel segments were analyzed 4 days after infection for luciferase and beta-galactosidase activity and for the extent of injury to the vessel wall. Luciferase activity in vessels infected using the double-balloon method was substantially greater than that achieved by catheter-based methods (P < .05). The dwell and double-balloon methods yielded selective expression in intimal cells, whereas arteries infected using perforated or Hydrogel-coated balloon catheters demonstrated expression primarily in medial cells. Tissue injury was most pronounced with the perforated balloon catheter. CONCLUSIONS: Prototype catheters permit relatively efficient direct gene transfer to vascular endothelium; however, delivery methods for targeting the medial cells are inefficient. Modifications are needed to optimize direct gene transfer and minimize tissue injury.

Coronary anatomy and prognosis of young, asymptomatic survivors of myocardial infarction.

PURPOSE: To assess the coronary anatomy and prognosis of young, asymptomatic survivors of myocardial infarction. PATIENTS AND METHODS: The records of all 5,316 patients who underwent cardiac catheterization at Parkland Memorial Hospital from July 1978 to December 1992 were reviewed to identify those patients 40 years old and younger who were catheterized within 60 days of a first myocardial infarction. Of 129 such patients, 48 had no indication for catheterization other than age (group I), and 81 were catheterized for spontaneous or provocable ischemia (group II). Extent of coronary artery disease and long-term follow-up were examined to ascertain the utility of cardiac catheterization in the asymptomatic patients. RESULTS: The 2 groups were similar with respect to clinical variables. The asymptomatic survivors of infarction (group I) had fewer diseased coronary arteries than did those with post-infarction ischemia (group II) (1.0 +/- 0.7 versus 1.5 +/- 1.0 [mean +/- SD] diseased coronary arteries, respectively; P = 0.002) and were less likely to have left-main or 3-vessel coronary artery disease (4% versus 20%, respectively; P = 0.027). Eighty-three percent of the group I patients had one diseased coronary artery, or less, and no patient underwent angioplasty or coronary bypass grafting on the basis of catheterization. After 71 +/- 44 months of follow-up, only 5 (10%) had died of a coronary-related event. CONCLUSIONS: Asymptomatic survivors of myocardial infarction who are 40 years of age or less rarely have left-main or 3-vessel coronary artery disease, and their long-term prognosis with conservative therapy is good. Routine catheterization in these patients is not warranted and should be reserved for those who manifest spontaneous or provocable post-infarction ischemia.

Predictive value of prominent pulmonary arterial wedge V waves in assessing the presence and severity of mitral regurgitation.

Indwelling pulmonary arterial catheters are often used to monitor and to guide therapy in critically ill patients. The magnitude of the V wave recorded from the pulmonary arterial wedge (PAW) position is sometimes used to assess the presence and severity of mitral regurgitation (MR). The present study was performed to assess the relation (or lack thereof) between a "prominent" PAW V wave and qualitative and quantitative estimates of MR. In 903 subjects (445 men and 458 women, aged 49 +/- 13 [mean +/- SD] years) referred for cardiac catheterization, an oximetrically confirmed PAW pressure was recorded with a large-lumen stiff catheter, and a left ventriculogram was recorded. In 646 of these subjects (328 men and 318 women, aged 50 +/- 13 years), forward cardiac output was measured by the Fick principle, and a regurgitant fraction was calculated. Prominent PAW V waves--as defined in several ways--were insensitive and had poor positive predictive value in identifying moderate or severe MR. At the same time, the absence of prominent PAW V waves was relatively specific for the absence of moderate or severe MR, and the negative predictive value of small V waves was very good. Thus, the prominence of a PAW V wave cannot be used to assess the presence or severity of MR.

Coronary-artery vasoconstriction induced by cocaine, cigarette smoking, or both.

BACKGROUND: In humans, the use of cocaine and cigarette smoking each increase the heart's metabolic need for oxygen but may also decrease the supply of oxygen. As cocaine abuse has proliferated, cocaine-associated chest pain, myocardial infarction, and sudden death have occurred, especially among smokers. We assessed the influence of intranasal cocaine and cigarette smoking, alone and together, on myocardial oxygen demand and coronary arterial dimensions in subjects with and subjects without coronary atherosclerosis. METHODS: In 42 smokers (28 men and 14 women; age, 34 to 79 years; 36 with angiographically demonstrable coronary artery disease), we measured the product of the heart rate and systolic arterial pressure (rate-pressure product) and coronary arterial diameters before and after intranasal cocaine at a dose of 2 mg per kilogram of body weight (n = 6), one cigarette (n = 12), or intranasal cocaine at a dose of 2 mg per kilogram followed by one cigarette (n = 24). RESULTS: No patient had chest pain or ischemic electrocardiographic changes after cocaine use or smoking. The mean (+/- SE) rate-pressure product increased by 11 +/- 2 percent after cocaine use (n = 30, P < 0.001), by 12 +/- 4 percent after one cigarette (n = 12, P = 0.021), and by 45 +/- 5 percent after both cocaine use and smoking (n = 24, P < 0.001). As compared with base-line measurements, the diameters of nondiseased coronary arterial segments decreased on average by 7 +/- 1 percent after cocaine use (P < 0.001), by 7 +/- 1 percent after smoking (P < 0.001), and by 6 +/- 2 percent after cocaine use and smoking (P < 0.001). The diameters of diseased segments decreased by 9 +/- 2 percent after cocaine use (n = 18, P < 0.001), by 5 +/- 5 percent after smoking (n = 12, P = 0.322), and by 19 +/- 4 percent after cocaine use and smoking (n = 12, P < 0.001). The increase in the rate-pressure product and the decrease in the diameters of diseased segments caused by cocaine use and smoking together were greater (P < 0.001 and P = 0.037, respectively) than the changes caused by either alone. CONCLUSIONS: The deleterious effects of cocaine on myocardial oxygen supply and demand are exacerbated by concomitant cigarette smoking. This combination substantially increases the metabolic requirement of the heart for oxygen but simultaneously decreases the diameter of diseased coronary arterial segments.

Frequency, cause and effect on operative outcome of depressed left ventricular ejection fraction in mitral stenosis.

To assess the incidence, pathophysiology and influence on operative outcome of a depressed left ventricular (LV) ejection fraction (EF) in patients with mitral stenosis (MS), demographic, hemodynamic and cineangiographic data on 72 patients (16 men, 56 women, aged 19 to 75 years) with isolated MS were reviewed. Of the 45 who had mitral commissurotomy or replacement, operative course and functional class before and after surgery were assessed. Of the 72 patients, 21 (29%) had an LVEF < or = 0.50. These 21 were similar to the 51 with an LVEF > 0.50 in age, gender, heart rate, intracardiac pressures, transvalvular gradient and valve area, but they had larger LV end-diastolic (79 +/- 19 [mean +/- SD] vs 59 +/- 15 ml/m2, p < 0.001) and end-systolic volumes (46 +/- 13 vs 23 +/- 8 ml/m2, p < 0.0001). Of the 45 subjects undergoing surgery, operative outcome was similar in the 14 with a depressed and the 31 with a normal LVEF. Thus, about 1/3 of patients with isolated MS have a depressed LVEF. Compared with those with MS and a normal LVEF, these subjects have hemodynamic derangements of similar severity, but they have larger LV end-diastolic and end-systolic volumes, suggesting that impaired LV contractile function or excessive afterload (rather than diastolic underfilling), or both, is the cause of a low LVEF. Those with an LVEF < or = 0.50 who undergo valve surgery have a similar operative outcome as those with an LVEF > 0.50.

Hydrogen inhalation for detecting intracardiac left-to-right shunting in adults.

The hydrogen inhalation technique is easily performed and exquisitely sensitive for detecting intracardiac left-to-right shunting. Previous studies of this technique relied heavily on data from infants and children, and the distinction between "normal" and "abnormal" was imprecise and somewhat arbitrary. The present study was done to assess the results of hydrogen inhalation in adults with and without intracardiac left-to-right shunting. In 45 adult subjects (15 men, 30 women, aged 18 to 72 years) (18 without and 27 with intracardiac left-to-right shunting), the elapsed time from hydrogen inhalation to its appearance in the pulmonary artery was measured. The 18 patients without shunting had an appearance time of 12 +/- 3 (mean +/- SD) seconds, and it was > or = 9 seconds in all. In contrast, the 27 subjects with shunting had an appearance time of 1.5 +/- 0.7 second, with only 1 of 27 being > or = 3 seconds. There was no relation between the magnitude of left-to-right shunting and the hydrogen appearance time. Thus, the hydrogen inhalation technique easily and reliably separates adult subjects with and without intracardiac left-to-right shunting, with no overlap between the 2 groups.

Effect of coronary angioplasty on late potentials one to two weeks after acute myocardial infarction.

In survivors of acute myocardial infarction (AMI), the restoration of anterograde flow in the infarct artery, even if accomplished beyond the time for myocardial salvage, may reduce the frequency of subsequent arrhythmic events and sudden death. Twelve subjects (8 men and 4 women, aged 39 to 69 years) with a first AMI, signal-averaged electrocardiographic late potentials, and an occluded infarct artery were prospectively identified. Seven (group I) had successful coronary angioplasty 6 to 15 days after AMI, and 5 (group II) were managed conservatively. Follow-up signal-averaged electrocardiography was performed 3 to 7 months later. From baseline to follow-up, the 7 group I subjects had a significant change in QRS duration (117 +/- 13 [mean + SD] to 102 +/- 10 ms), root-mean-square voltage (10.4 +/- 4.7 to 31.0 +/- 7.6 microV), and low-amplitude signal duration (47.5 +/- 8.5 to 32.4 +/- 5.2 ms) (p < or = 0.05 for all 3 variables). No group I patient had a late potential at follow-up. In contrast, the 5 group II patients showed no change in QRS duration or low-amplitude signal duration from baseline to follow-up, and all 5 had a late potential at follow-up. At follow-up, the root-mean-square voltage was significantly greater and the low-amplitude signal and QRS durations significantly less in group I than in group II (p < 0.05 for all 3 variables). Thus, in our patients, the mechanical restoration of anterograde perfusion in an occluded infarct artery 1 to 2 weeks after AMI caused the resolution of signal-averaged electrocardiographic late potentials.

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.

Are contraction and relaxation coupled in patients with and without congestive heart failure?

BACKGROUND: Although changes in contractility are often accompanied by changes in relaxation, a mathematical model of ventricular coupling has not been described. A model we examined suggests a hyperbolic relation between measurements of contraction and relaxation. We thus tested the hypothesis that relatively load-independent measurements of contractility (end-systolic elastance [Ees]) and relaxation (the slope of the tau-to-end-systolic pressure relation [R]) were coupled. METHODS AND RESULTS: To establish the validity of the model, an assessment of Ees and R was made in 30 subjects who underwent sequential digital ventriculography and micromanometer pressure measurements during atrial pacing (93 +/- 10 min-1) before and after graded doses of nitroprusside. To establish if a cyclic AMP (cAMP)-mediated intervention alters coupling, seven of the 30 subjects were studied before and after 3 months of beta-blockade. To determine if a non-cAMP-mediated intervention alters coupling, 12 other patients were studied before and after deslanoside. Nonlinear regression analysis for the initial 30 patients suggested a hyperbolic relation: (Ees) (R) = 1.05 (r = 0.79, p less than 0.001) with an inflection point near Ees = 1.02 mm Hg/ml. Thus, with normal or near-normal contractility, relaxation is normal and not load dependent (R is close to 0). With systolic dysfunction, relaxation becomes very afterload dependent and so must be normalized for load. After long-term beta-blockade in patients with severe left ventricular dysfunction, small improvements in contractility (elastance) occurred with larger changes in relaxation, but the curve describing the relation was not displaced. Acute administration of deslanoside resulted in a large increase in elastance and a smaller change in relaxation but did not alter coupling. However, the magnitude of the change in R was dependent on the predrug R value. CONCLUSIONS: These data suggest contraction and relaxation may be physiologically coupled with relaxation relatively preserved in early heart failure and more rapid deterioration in relaxation as elastance falls under 1.02 mm Hg/ml. Both beta-blockers (which may act through cAMP) and digitalis (which is cAMP independent) improve contraction and relaxation, but both mechanisms appear to maintain coupling. The hyperbolic relation between contraction and relaxation may have important implications regarding therapeutic response and selection of patients for clinical trials in heart failure.

Collection and handling of clinical blood samples to assure the accurate measurement of cocaine concentration.

The measurement of serum cocaine concentration is difficult because it is rapidly metabolized in vivo and in vitro. Previous investigators have used sodium fluoride (0.5-3.0%) in an attempt to stabilize its concentration in samples of whole blood, but these concentrations of sodium fluoride are not readily available outside the analytical laboratory. This study was performed to assess the stability of cocaine in whole blood when stabilized in a commonly available concentration of sodium fluoride (0.25%), with or without concomitant refrigeration. Whole blood was enriched with cocaine to a final concentration of 900 ng/mL and added to flasks containing sodium fluoride (0, 0.25, 0.5, and 1.0%) or 0.25% sodium fluoride plus potassium oxalate (gray-top Vacutainer tubes), after which it was stored at 4 degrees C or at room temperature. Whole blood cocaine concentrations were measured at 0, 24, and 48 h by gas chromatography. Sodium fluoride at all concentrations, with or without refrigeration and potassium oxalate, effectively inhibited cocaine degradation, with 86-91% of the drug present after 48 h. In contrast, substantial degradation of cocaine occurred in the samples stored without sodium fluoride, regardless of temperature. Thus, the use of commercial gray-top Vacutainer tubes effectively stabilizes cocaine in blood during procurement, transport, and short-term storage.

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.