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.

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.

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.

In vivo nuclear magnetic resonance imaging of myocardial perfusion using the paramagnetic contrast agent manganese gluconate.

Previous nuclear magnetic resonance (NMR) imaging studies have indicated that coronary occlusion does not produce sufficient changes in standard tissue relaxation times to allow the detection of acute ischemia. To identify acute myocardial perfusion abnormalities, the use of the paramagnetic agent manganese gluconate combined with calcium gluconate (MnGlu/CaGlu) was investigated in canine models of acute coronary artery occlusion. In vitro studies showed that MnGlu/CaGlu was a more efficient relaxing agent than gadolinium-DTPA (relaxivity of 7.8 versus 5.1 s-1 mM-1) and demonstrated affinity for normal myocardium. The distribution of MnGlu/CaGlu as measured by manganese-54 tracer studies was proportional to myocardial blood flow in both normal and ischemic tissue. Hearts excised from dogs after coronary artery occlusion and administration of 0.035 mM/kg MnGlu/CaGlu were imaged ex vivo using a relatively spin-lattice relaxation time (T1)-weighted gradient reversal technique (repetition time [TR] 50 ms and echo time [TE] 9 ms). These images showed increased signal intensity in the normally perfused myocardium with a mean signal intensity ratio of hypoperfused to normal myocardium of 0.55 +/- 0.12 (mean +/- SD). In vivo images obtained in nine dogs after coronary artery occlusion and administration of the same dose of MnGlu/CaGlu demonstrated the region of hypoperfused myocardium in six dogs with a signal intensity ratio of hypoperfused to normal myocardium of 0.64 +/- 0.23 (p less than 0.05 versus control). When a higher dose of 0.1 mM/kg MnGlu/CaGlu was utilized and in vivo imaging was performed using a relatively spin-spin relaxation time (T2)-weighted (TR gated, TE 60 ms) spin-echo sequence in six dogs, the signal intensity of normal myocardium was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Influence of labetalol on cocaine-induced coronary vasoconstriction in humans.

PURPOSE: Although labetalol is sometimes given to patients with cocaine-associated chest pain, its influence on cocaine-induced coronary vasoconstriction is unknown. PATIENTS AND METHODS: In 15 patients (7 men, 8 women, aged 40 to 79 years) undergoing catheterization for chest pain, heart rate, mean arterial pressure, and coronary arterial area (by computer-assisted quantitative angiography) were measured (1) at baseline, (2) 15 minutes after intranasal cocaine, 2 mg/kg, then (3) 5 minutes after intravenous saline (n = 6) or labetalol, 0.25 mg/kg (n = 9). RESULTS: Of 40 coronary arterial segments analyzed, cocaine induced a 13% +/- 10% (mean +/- standard deviation) decrease in coronary arterial area in 32. Subsequently, no variable changed after saline administration. Although labetalol reduced mean arterial pressure (117 +/- 14 mm Hg after cocaine, 110 +/- 11 mm Hg after labetalol; p < 0.05), it induced no change in the coronary arterial area (3.47 +/- 1.37 mm2 after cocaine, 3.37 +/- 1.32 mm2 after labetalol; p = NS). CONCLUSION: Labetalol reverses the cocaine-induced rise in mean arterial pressure, but does not alleviate cocaine-induced coronary vasoconstriction.

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.

The natural history of isolated left ventricular diastolic dysfunction.

STUDY OBJECTIVE: To assess the natural history of isolated left ventricular diastolic dysfunction. PATIENTS AND METHODS: Follow-up (average duration, 68 months) was obtained in 51 patients with isolated left ventricular diastolic dysfunction at cardiac catheterization, characterized by (1) an elevated left ventricular end-diastolic pressure; (2) normal left ventricular end-diastolic and end-systolic volumes; (3) normal left ventricular ejection fraction; (4) no coronary artery disease; and (5) no valvular disease. RESULTS: During follow-up, seven patients died, but only one died of cardiac causes. Of the 44 living subjects, 20 (45%) noted new-onset symptoms of congestive heart failure, with 11 (25%) of these requiring hospitalization, and 12 (27%) required hospitalization for recurrent chest pain. CONCLUSIONS: Isolated left ventricular diastolic dysfunction is associated with a low cardiac mortality; at the same time, however, it is associated with substantial morbidity.

Dosing of contrast material to prevent contrast nephropathy in patients with renal disease.

PURPOSE: Contrast-induced renal dysfunction has been reported to occur in 15% to 42% of patients with underlying azotemia, but there is disagreement as to whether its incidence is reduced by limiting the amount of contrast material. To adjust the amount of contrast material to the severity of azotemia, we have utilized the following formula to calculate a contrast material "limit" in patients with renal disease: Contrast material limit = (formula; see text) PATIENTS AND METHODS: Over a 10-year period, 115 patients (53 men, 62 women, aged 61 +/- 11 [mean +/- SD] years) with renal dysfunction (baseline serum creatinine level greater than or equal to 1.8 mg/dL) underwent cardiac catheterization and angiography, after which the level of serum creatinine was measured daily for five days. The amount of contrast material that was given adhered to the limit in 86 patients (Group I) and exceeded it in 29 (Group II). RESULTS: Contrast-induced renal dysfunction (an increase in serum creatinine greater than or equal to 1.0 mg/dL) occurred in two (2%) patients in Group I and in six (21%) patients in Group II (p less than 0.001). Of the 48 patients with concomitant diabetes mellitus, the contrast limit was surpassed in 16, six (38%) of whom had contrast nephropathy. Only two of the 32 (6%) diabetic patients in whom the contrast limit was not exceeded had contrast nephropathy (p less than 0.001). CONCLUSIONS: Thus, contrast-induced renal dysfunction occurs infrequently if the amount of contrast material is limited in accordance with the degree of azotemia. Diabetic patients have a high incidence of contrast nephropathy, particularly when they receive an excessive amount of contrast. In patients with diabetes and renal impairment, it may be preferable to perform angiography as a staged procedure or to utilize alternative (non-contrast) techniques to obtain the desired information rather than to exceed the prescribed contrast limit.

Underestimation of cardiac output by thermodilution in patients with tricuspid regurgitation.

INTRODUCTION: This study was done to assess the accuracy and reliability of the thermodilution technique in measuring cardiac output in patients with tricuspid regurgitation. PATIENTS AND METHODS: In 30 subjects (17 men, 13 women, aged 50 +/- 14 [mean +/- SD] years), cardiac output was measured in close temporal proximity by thermodilution as well as Fick or indocyanine green dye, after which the presence and severity of tricuspid regurgitation were assessed by contrast right ventriculography or pulsed Doppler echocardiography. RESULTS: In the 13 patients without tricuspid regurgitation, there was excellent agreement between the results of thermodilution and Fick or indocyanine green dye cardiac output determinations (4.95 +/- 1.19 liters/minute by thermodilution, 4.90 +/- 1.11 liters/minute by Fick or indocyanine green dye; NS). In contrast, in the 17 patients with tricuspid regurgitation, the results of thermodilution were consistently lower than those of Fick or indocyanine green dye (4.22 +/- 1.45 liters/minute by thermodilution, 4.99 +/- 1.67 liters/minute by Fick or indocyanine green dye; p less than 0.001). CONCLUSION: Thus, the thermodilution technique of measuring cardiac output is inaccurate in patients with tricuspid regurgitation, yielding results that are consistently lower than the actual outputs.

Influence of intranasal cocaine on plasma constituents associated with endogenous thrombosis and thrombolysis.

PURPOSE: As cocaine abuse has become widespread, catastrophic cocaine-associated cardiovascular events have been noted with increasing frequency. Although these incidents are thought to be caused by drug-induced vasoconstriction and/or arterial thrombosis, the influence of cocaine on the plasma constituents involved in endogenous thrombosis and thrombolysis has not been characterized. PATIENTS AND METHODS: In 22 patients (8 men, 14 women, ages 32 to 62 years) undergoing cardiac catheterization, blood samples were procured before and 15 minutes after the administration of intranasal saline (n = 8, controls) or cocaine, 2 mg/kg (n = 14), and the plasma concentrations of fibrinogen, plasminogen, and lipoprotein(a), as well as tissue plasminogen activator activity and plasminogen activator inhibitor (PAI-1) activity, were measured. RESULTS: No variable changed with the use of intranasal saline, whereas the use of cocaine resulted in an increase in PAI-1 activity (0.48 + 0.06 [mean + SD] nmol/L at baseline, 0.53 + 0.05 nmol/L after cocaine, P = 0.011). CONCLUSION: Intranasal cocaine administration is associated with an increase in plasma PAI-1 activity. This may be important in recreational users of cocaine who experience vascular thrombosis.

Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions.

PURPOSE: Nicotine replacement therapy has become a popular therapy for smokers attempting to stop smoking. Unfortunately, some subjects continue to smoke while receiving it. Since nicotine is believed to be the primary constituent of cigarette smoke responsible for its acute adverse effects on myocardial oxygen supply and demand, concomitant nicotine replacement therapy and smoking theoretically could provoke a marked decrease in myocardial oxygen supply and increase in demand. This study was performed to assess the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) myocardial oxygen demand, (b) coronary arterial dimensions, and (c) the development of acute cardiovascular tolerance. PATIENTS AND METHODS: In 19 smokers referred for cardiac catheterization for the evaluation of chest pain, we assessed the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) heart rate-systolic arterial pressure product (an estimate of myocardial oxygen demand), (b) coronary arterial dimensions (measured with computer-assisted quantitative arteriography), and (c) the development of acute cardiovascular tolerance. RESULTS: Smoking a first cigarette increased rate pressure product (P < 0.001) and decreased coronary arterial dimensions (P < 0.0001). Subsequently, neither variable was altered by intranasal nicotine spray or a second cigarette. Despite a substantial increase in serum nicotine concentration with nicotine spray and smoking, acute cardiovascular tolerance appears to develop. CONCLUSIONS: Cigarette smoking causes an increase in myocardial oxygen demand and concomitant coronary arterial vasoconstriction. However, further increases in the serum nicotine concentration do not cause a greater increase in demand or decrease in coronary arterial dimensions. These data suggest that humans acutely develop tolerance to an increasing nicotine concentration, thereby helping to explain the apparent lack of a potential synergistic adverse effect associated with continued smoking during nicotine replacement therapy.

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.