Heart muscle viability following hypoxia: protective effect of acidosis.

The mechanical performance of hypoxic heart muscle is further depressed by an acid pH. In contrast to preparations at normal or alkaline pH. however, hypoxic preparations at acid pH do not develop contracture and exhibit full recovery of mechanical activity upon reoxygenation.

Protein-bound homocyst(e)ine. A possible risk factor for coronary artery disease.

The development of atherosclerotic changes and thromboembolism are common features in homocystinurics. Hence, we postulate a positive correlation between the level of homocyst(e)ine in the blood and the occurrence of coronary artery disease. Homocysteine is found either as free homocystine, cysteine-homocysteine mixed disulfide, or protein-bound homocyst(e)ine. In nonhomocystinuric subjects, most homocysteine molecules are detectable in the protein-bound form. Thus, protein-bound homocyst(e)ine in stored plasma which reflected total plasma homocyst(e)ine was determined in 241 patients with coronary artery disease (173 males and 68 females). The mean +/- SD total plasma homocyst(e)ine was 5.41 +/- 1.62 nmol/ml in male patients, 4.37 +/- 1.09 nmol/ml in male controls, 5.66 +/- 1.93 nmol/ml in female patients, and 4.16 +/- 1.62 nmol/ml in female controls. The differences between the patients with coronary artery disease and the controls were statistically significant (P less than 0.0005).

Effects of altering carbohydrate metabolism on energy status and contractile function of vascular smooth muscle.

Substrate-dependent changes in vascular smooth muscle energy metabolism and contractile function were investigated in isolated porcine carotid arteries. In media containing glucose glycogen catabolism accounted for all the estimated high-energy phosphate turnover that occurred in conjunction with contraction induced by 80 mM KCl. However, in glucose-free media glycogen catabolism accounted for only a portion of the estimated ATP utilization in resting and contracting arteries, even though glycogen stores were not depleted. The glycogenolysis and lactate production that ordinarily accompanies contraction was completely inhibited by 5 mM 2-deoxyglucose (2-DG). However, there was no decrease in the high-energy phosphate levels when compared to control resting arteries similarly treated with 2-DG. The results suggest that an endogenous non-carbohydrate source may be an important substrate for energy metabolism. Treatment of arteries with 50 microM iodoacetate (IA) in media containing glucose resulted in a marked reduction of high energy phosphate levels and an accumulation of phosphorylated glycolytic intermediates, as demonstrated by 31P-NMR spectroscopy. In glucose-free media, 50 microM IA had only a slight effect on high-energy phosphate levels, while glycogenolysis proceeded unhindered. With 1 mM IA in glucose-free media, the oxidative metabolism of glycogen was inhibited as evidenced by the depletion of high-energy phosphates and the appearance of sugar phosphates in the 31P-NMR spectra. Thus, the titration of enzyme systems with IA reveals a structural partitioning of carbohydrate metabolism, as suggested by previous studies.

Determination of cardiac output in critically ill patients by dual beam Doppler echocardiography.

Recent technology in Doppler echocardiography has produced a dual beam Doppler instrument that is capable of insonating the total cross-sectional area of the ascending aorta. The purpose of this study was to evaluate the accuracy of this instrument in measuring cardiac output in critically ill patients by comparing results with those of the thermodilution-derived cardiac output. A technically adequate Doppler cardiac output measurement was attained in 71 (91%) of 78 patients. The range of thermodilution-derived cardiac output measurements was from 1.58 to 11.70 liters/min. To maximize thermodilution cardiac output reliability, several measurements were made for each patient. Those patients in whom the difference between the highest and lowest measurement varied by less than 10% from the averaged results were accepted into the 50 patient study. There was significant correlation between dual beam Doppler- and thermodilution-derived cardiac output (r = 0.96, SEE = 0.55 liters/min, p less than 0.0001). This study demonstrates that dual beam Doppler ultrasound is a promising noninvasive method of measuring cardiac output in the critically ill patient.

Adult cardiology and the expanding supply of physicians.

The number of cardiologists can be projected with considerable accuracy into the next century. The total cardiology pool of physicians will increase until the year 2015 at which time those entering and leaving the pool will come into equilibrium. At that time the ratio of active cardiologists to the population will have greatly increased. This nation's future need for cardiologists is difficult to assess with any degree of precision. Therefore, this is the time for updating practice profile studies. Such studies today could be formulated in a manner to provide more detailed information on the cardiologist's daily activities. In addition, a data base developed through methodology such as the consensus formation approach must be developed and updated on a periodic basis. Through such analyses it will be possible to quantitate the future needs of cardiovascular manpower.

Diaphragmatic left ventricular aneurysm. Clinical features, surgical treatment, and long-term follow-up in 22 patients.

Although the formation of a left ventricular aneurysm (LVA) is a common and well-recognized complication of myocardial infarction (MI), diaphragmatic LVA is a rare clinical entity. Of 354 consecutive patients who underwent LVA resection, we describe the clinical features and surgical results of 22 patients (6%) with diaphragmatic LVA. All patients had a history of MI. The principal clinical indication for surgery was heart failure in nine patients, angina pectoris in ten patients, and recurrent ventricular tachycardia unresponsive to medical therapy in three patients. A ventricular septal defect was present in two patients, and moderate to severe mitral regurgitation was present in four patients. Three of the four surgical deaths (operative mortality, 18%) occurred in patients with mitral regurgitation or with ventricular septal defect. Eleven patients are alive at a mean follow-up of 40 months. Six of them are asymptomatic and two have angina at a higher level of physical activity than before surgery. Notable differences exist in the clinical presentation and surgical findings between patients with diaphragmatic and anterior LVA.

Effects of hypoxia, cyanide, and ischaemia on myocardial contraction: observations in isolated muscle and intact heart.

Using potassium cyanide (KCN) to stimulate hypoxia, the effects of intracoronary injections of KCN were compared with total occlusions of the same vessel. Imparied contraction as measured by segment length gauges was of equally abrupt onset following both interventions. The magnitude of systolic expansion at one minute was more marked following total occlusion than after KCN administration.

31P-nuclear magnetic resonance analysis of extracts of vascular smooth muscle.

31P-nuclear magnetic resonance spectroscopy was used to assess phosphate metabolites in perchloric acid extracts of rabbit aorta. In addition to the high energy phosphates, several other phosphorus compounds were detected and quantified. Most notable was the presence of a prominent phosphomonoester compound appearing at a chemical shift of 3.86 delta. This compound constituted 26% of the total extractable tissue phosphorus and is tentatively identified as ribose-5-phosphate, a pentose phosphate pathway intermediate. While ATP and phosphocreatine did not change during glucose and oxygen deprivation or during prolonged muscle contraction, the 3.86 delta phosphate decreased significantly. Furthermore, theophylline, an agent that increases intracellular cAMP, also decreased the level of the 3.86 delta phosphate. These results are consistent with the concept that intermediate metabolism sustains high energy phosphate pools in vascular smooth muscle in the steady state under various conditions. The pentose phosphate pathway may play an important role in vascular smooth muscle metabolism.

Significance of ventricular tachycardia in idiopathic dilated cardiomyopathy: observations in 35 patients.

To evaluate the significance of ventricular tachycardia (VT) in idiopathic dilated cardiomyopathy (IDC), 35 consecutive patients seen between 1976 and 1980 were studied. The criteria for diagnosis of IDC were based on clinical, laboratory, and cardiac catheterization findings. All patients had right and left heart catheterization, left ventriculography, and coronary cineangiography. Long-term ambulatory electrocardiograms (Holter) were obtained in all patients at the time of diagnosis. There were 24 male and 11 female patients aged 22 to 72 years (mean +/- standard deviation [SD]51 +/- 12). Frequent ventricular premature beats (VPB) (30/h) were observed in 29 patients (83%): complex VPB (Lown grades 3, 4, and 5) in 93% and simple VPB in 7%. Twenty-one patients (60%) had nonsustained VT consisting of 3 to 46 beats (8 +/- 5) with rates from 75 to 210/min. No difference between patients with and those without VT was observed in regard to the presenting symptoms, functional classification, electrocardiographic findings, heart size on chest X-ray, and the hemodynamic measurements including cardiac index, left ventricular end-diastolic pressure, and ejection fraction. Patients with VT were older (p less than 0.05). Follow-up observation from 4 to 74 months (34 +/- 17) showed that 2 patients died suddenly (1 with and 1 without previous VT), a third patient died from intractable congestive heart failure, and the fourth from sepsis. It is concluded that (1) the incidence of ventricular arrhythmias in IDC is high, (2) VT is frequent and tends to occur in the nonsustained form, and (3) there is no correlation between VT and the clinical and hemodynamic findings. VT does not appear to predict prognosis during a relatively short follow-up period in patients with IDC.

Internal mammary arteriovenous malformation with communication to the pulmonary vessels.

A 25 year old asymptomatic man with a past history of pulmonary tuberculosis presented with a continuous murmur. Selective arteriography revealed a left internal mammary arteriovenous malformation in communication with vessels in the left upper pulmonary lobe. No significant hemodynamic abnormalities were detected. This is the 26th reported case of internal mammary arteriovenous fistula and the 6th with a pulmonary communication. Review of the data in previous cases suggests that surgical indications are limited to symptomatic relief, heart failure during infancy or the possible risk of endarteritis, proximal arterial degeneration or rupture.

Relation of ventricular premature beats to underlying heart disease.

The relation between ventricular premature beats (VPBs) and physiologic disease was investigated in 305 patients who had 24-hour Holter monitoring tests, cardiac catheterization and angiography. Both frequency and Lown class of VPBs were measured. Analyses showed that occurrence of VPBs at an average frequency of more than 2 per hour or occurrence of complex VPBs (Lown class greater than 2) have the highest association with the presence and severity of cardiac disease. Using these criteria, VPB severity was then compared with extent of ventricular wall motion abnormality (right anterior oblique projection segments), ejection fraction, end-diastolic pressure, category of disease (normal, coronary artery disease [CAD], valvular heart disease, dilated cardiomyopathy), age and severity of CAD (major coronary arteries with greater than 75% diameter reduction). Severe VPBs defined either by complexity or frequency were significantly correlated with extent of wall motion abnormality, ejection fraction, category of disease and age. Severe VPBs were not significantly correlated with end-diastolic pressure or severity of CAD. Discriminant analysis then showed that in addition to wall motion abnormality and ejection fraction, category of disease and age are independently correlated with VPB severity.

Occlusive disease confined to the right coronary artery: clinical features, surgical treatment and long-term follow-up in 124 patients.

The clinical presentation and surgical results in 124 consecutive patients who underwent aorta to right coronary arterial bypass surgery from January 1970 through June 1977 were reviewed. Preoperatively, 75 percent of the patients were in New York Heart Association functional class III or IV, 9 percent presented with unstable angina and 5 percent had life-threatening ventricular arrhythmias. All patients had high grade occlusive disease confined to the right coronary artery; 34 percent of the patients had associated nonsignificant disease (less than 50 percent intraluminal narrowing) of the left anterior descending or circumflex artery. Left ventricular function was normal in 63 percent and minimally impaired in 37 percent. The operative mortality rate was 1.6 percent. The course of the 122 survivors was followed up for 3.7 years. There were four late deaths, and the 5 year mortality rate was 4.0 percent. Eight patients were reoperated on because of recurrence of symptoms and occlusion of the graft or progression of occlusive disease of the other major coronary arteries, or both. Of the remaining 110 patients, 98 are either in functional class I or II, 60 are taking no cardiovascular medications, 52 are working full time without angina nad 73 are asymptomatic. In summary, bypass surgery for isolated right coronary artery disease has a low mortality rate and results in excellent long-term symptomatic improvement.

Efficacy of coronary bypass grafting in exercise-induced ventricular tachycardia.

The effects of coronary bypass grafting on ventricular tachycardia induced by treadmill stress testing (TST) were analyzed in nine patients by repeating the test an average of 5 months after operation. Preoperatively, eight patients experienced pain and all had ischemic ST-segment depression during exercise. Six patients had a single episode and two patients had multiple episodes of ventricular tachycardia; in one patient ventricular tachycardia degenerated into ventricular flutter necessitating direct-current cardioversion. Postoperatively, time of exercise and double product were significantly higher during TST. Electrocardiographic ischemic changes were present in only two patients and ventricular tachycardia was not observed. All patients are alive and average of 24 months after the operation, and eight of them are asymptomatic. In conclusion, among patients with coronary artery disease who have exercise-induced ventricular arrhythmias, myocardial revascularization is associated with improvement of exercise capacity and suppression of arrhythmias.

Myocardial imaging with 134mCesium. Comparison of scintigraphic and cineradiographic results.

Thirty-four patients had noninvasive myocardial perfusion imaging at rest using 134mCs. The results were compared with the results of coronary cineangiography and left ventriculography. All 21 patients who had abnormal left ventriculograms had corresponding myocardial imaging defects. This group included 14 patients with electrocardiographic evidence of either an old inferior, anteroseptal, anterior, or anterolateral myocardial infarction. Thirteen patients had normal left ventriculograms: this group included 6 patients with 75% or greater obstruction of one or more coronary arteries and 7 patients with normal or insignificantly diseased vessels. Only 2 of these patients had abnormal myocardial images: both had severe obstruction of the proximal left anterior descending artery without collateral filling of this vessel. In the resting patient who has 134mCs myocardial imaging, we concluded that we primarily are visualizing varying degrees of scarred myocardium rather than reversibly ischemic myocardium.

Regional myocardial metabolism during subtotal and total coronary artery occlusion.

Regional myocardial metabolism was examined by means of coronary venous sampling in dogs having acute nonsimultaneous occlusions of the left anterior descending (LAD) and circumflex (CIRC) coronary arteries. Regional coronary venous metabolic sampling was not found to separate ischemic from nonischemic myocardium in LAD occlusion and did so imperfectly in isolated CIRC occlusion. Myocardial metabolic consequences of subtotal and total coronary artery occlusion were compared in dogs during LAD and CIRC occlusion and in human subjects with subtotal and total anterior coronary artery occlusion. In spite of ECG evidence of greater myocardial ischemia during total coronary artery occlusion in the dog, transmyocardial metabolic changes were more consistent during subtotal occlusion. Human subjects stressed during cardiac catheterization exhibited a similar apparent paradox. This suggests variable coronary venous washout from ischemic myocardium during total coronary artery occlusion and, in humans, may also reflect the presence of scar tissue. Caution is advised when interpreting myocardial metabolic information in the presence of total coronary artery occlusion, since underestimation of the extent of myocardial ischemia is more likely than with an occlusion of lesser degree.

Findings on routine right heart catheterization in patients with suspected coronary artery disease.

Whether catheterization of the right heart should be performed routinely in all patients undergoing coronary angiography for assessment of coronary artery disease is controversial. To objectively assess the utility of routine right heart catheterization, hemodynamic data from 2,178 patients studied for angina having no signs, symptoms, or history of congestive heart failure were analyzed retrospectively. The salient results are as follows: 0.9% patients had unsuspected mitral valve gradients greater than or equal to 5 mm Hg; 0.4% had occult left-to-right shunts; 1% had pulmonary hypertension (pulmonary artery systolic pressure greater than or equal to 40 mm Hg) not attributable to an elevated mean pulmonary capillary wedge pressure (PCWP); 4.8% had PCWP greater than or equal to 18 mm Hg; 6% had cardiac indexes less than or equal to 2.0 L/min/m2, suggesting subclinical left ventricular failure. Overall, 14.5% of patients had at least one abnormal right-sided hemodynamic variable revealed by right heart catheterization. The frequency of abnormalities increased with increasing Canadian Cardiovascular Society grade of angina. Ten percent of grade 1, 14% of grade 2, 15% of grade 3, and 19% of patient 4 patients had at least one abnormality (phi 2 test, p less than or equal to 0.005). It is concluded that the right heart catheterization adds an important dimension to the diagnosis and treatment of patients undergoing coronary angiography for assessment of coronary artery disease and might significantly influence subsequent patient management.