Blood Pressure Times Heart Rate Research Articles

Modeling to Link Regional Myocardial Work, Metabolism and Blood Flows

Given the mono-functional, highly coordinated processes of cardiac excitation and contraction, the observations that regional myocardial blood flows, rMBF, are broadly heterogeneous has provoked much attention, but a clear explanation has not emerged. In isolated and in vivo heart studies the total coronary flow is found to be proportional to the rate-pressure product (systolic mean blood pressure times heart rate), a measure of external cardiac work. The same relationship might be expected on a local basis: more work requires more flow. The validity of this expectation has never been demonstrated experimentally. In this article we review the concepts linking cellular excitation and contractile work to cellular energetics and ATP demand, substrate utilization, oxygen demand, vasoregulation, and local blood flow. Mathematical models of these processes are now rather well developed. We propose that the construction of an integrated model encompassing the biophysics, biochemistry and physiology of cardiomyocyte contraction, then combined with a detailed three-dimensional structuring of the fiber bundle and sheet arrangements of the heart as a whole will frame an hypothesis that can be quantitatively evaluated to settle the prime issue: Does local work drive local flow in a predictable fashion that explains the heterogeneity? While in one sense one can feel content that work drives flow is irrefutable, the are no cardiac contractile models that demonstrate the required heterogeneity in local strain-stress-work; quite the contrary, cardiac contraction models have tended toward trying to show that work should be uniform. The object of this review is to argue that uniformity of work does not occur, and is impossible in any case, and that further experimentation and analysis are necessary to test the hypothesis.

Clarifying the Obesity Paradox

When compared to ideal weight patients, obese patients have a higher prevalence of CHF but a better prognosis once CHF or a cardiac abnormality has occurred, hence the Obesity Paradox. This report compares obese patients with ideal weight patients using cardiopulmonary exercise testing and echo-doppler studies to evaluate differences that would help explain the obesity paradox. Patients referred to an outpatient cardiology clinic for exercise testing were evaluated. Patients were selected who had <86% of their predicted exercise capacity measured by VO2. Predictions were corrected for age, sex, and weight. All patients were limited by their cardiac performance. Patients with primary valve disease and renal failure were excluded. Patients were divided into 2 groups based upon BMI<25 (ideal) and BMI>30 (obese). They were also matched for analysis based upon their % reduction in exercise performance. Each group had a mean reduction of 70%. The results were compared using a paired t-test.Tabled 1FindingsAGE (years)%RWMASBP X HRRWTVE/VCO2DT* (ms)SBP (mmHg)N=40403137351631OBESE(MEAN)62.53294100.4629.3276.5151.7OBESE(ST DEV.)17.28.954630.084.2591.622.6IDEAL(MEAN)59.51523174.4132.3225.9138.7IDEAL(ST.DEV.)17.23257970.085.653.325.4P VALUENS0.020.00030.0090.0070.0450.01%RWMA=% resting wall motion abnormality, SBP X HR=systolic blood pressure times heart rate at maximal exercise, RWT=relative wall thickness, VE/VCO2=liters of ventilation required to eliminate a liter of carbon dioxide at anaerobic threshold, DT=Doppler deceleration time for Mitral valve flow *=patients with abnormal diastolic function as measured by left atrial area>19 or VE/VCO2>32. Open table in a new tab Ideal patients have greater resting systolic dysfunction, impaired respiratory function, and decreased myocardial O2 consumption while obese patients have more hypertension and concentric hypertrophy. In patients with diastolic dysfunction, ideal patients have shorter DT suggesting increased left atrial diastolic pressure. Conclusion: These data suggests ideal patients have greater cardiac involvement than obese patients when matched by % decrease in functional capacity. This relationship may contribute to the obesity paradox. %RWMA=% resting wall motion abnormality, SBP X HR=systolic blood pressure times heart rate at maximal exercise, RWT=relative wall thickness, VE/VCO2=liters of ventilation required to eliminate a liter of carbon dioxide at anaerobic threshold, DT=Doppler deceleration time for Mitral valve flow *=patients with abnormal diastolic function as measured by left atrial area>19 or VE/VCO2>32.

Pressure–heart rate product changes from childhood to adulthood in a biracial population — a crossover phenomenon: the Bogalusa Heart Study

Cardiovascular (CV) hemodynamic characteristics are major risk factors for heart disease. Cross-sectional surveys of 5,976 individuals (47% males; 63% Whites), aged 4 to 44 years, and a subset of 1,365 individuals examined both in childhood and in adulthood were examined for blood pressure and heart rate along with cardiovascular risk factors. In early childhood, Whites showed significantly faster heart rate than Blacks; at adolescence, blood pressure levels became greater in Blacks. The systolic blood pressure times heart rate, the double product, in childhood (Whites > Blacks) is reversed in adulthood (Blacks > Whites). A “crossover” at the young adult age occurs. The crossover was observed at around 20 years in females and 25 years in males. Multivariate analyses indicated age, race, and homeostasis model of insulin resistance were independently related to the double product. Further, there was a significant interaction between age and race. These hemodynamic parameters change with increasing age with a crossover pattern of the pressure-rate product between the different races in young adults. Changes in the double product suggest a greater sympathetic nervous system activation occurring in Blacks reaching adulthood. Although not measured, central vs. peripheral sympathetic–parasympathetic balance, which determine hemodynamic characteristics, is influenced by increasing obesity and carbohydrate-insulin metabolic changes in adulthood. Further, hemodynamic parameters create a cardiovascular burden over time producing subtle, subclinical disease of the cardiovascular system. Control of obesity in the population remains critical.

Aggravation of angina pectoris by two percent carboxyhemoglobin

A double-blind, randomized, crossover study was performed in 15 patients with stable angina to evaluate the effect of breathing carbon monoxide (CO), which raised the carboxyhemoglobin (COHb) from 1.09% to 2.02%, versus breathing compressed, purified air, which lowered the COHb from 1.07% to 1.00% on exercise duration until angina. The exercise duration until angina was 324.5 seconds in the air control period and 330.3 seconds after purified air compared to 321.7 seconds in the CO air control period and 289.7 seconds after CO. Breathing CO to raise the COHb from 1.09% to 2.02% caused a decrease in exercise duration until angina pectoris ( p < 0.001) and a reduction in product of systolic blood pressure times heart rate at the onset of angina ( p < 0.001). These data indicate that a 2% COHb level aggravates angina pectoris due to coronary artery disease.

Effect of non-nicotine cigarettes and carbon monoxide on angina.

The effect of smoking five non-nicotine cigarettes and of breathing carbon monoxide on exercise-induced angina was evaluated in 12 patients with angina. Smoking increased venous carboxyhemoglobin from 1.71 to 5.35%, decreased exercise duration until angina 45%, increased ischemic ST-segment depression at angina from 1.33 to 1.52 mm, and decreased systolic blood pressure times heart rate at angina. Breathing carbon monoxide increased venous carboxyhemoglobin from 1.73 to 5.37%, decreased exercise duration until angina 35%, increased ischemic ST-segment depression at angina from 1.31 to 1.50 mm, and decreased systolic blood pressure times heart rate at angina. Greater decreases in exercise duration until angina and in systolic blood pressure times heart rate at angina (p less than 0.001) were observed after smoking than after breathing carbon monoxide. Tobacco components other than nicotine or carbon monoxide are responsible for a small decrease in exercise performance until angina.

Effect of prazosin vs placebo on chronic left ventricular heart failure.

The effect of the vasodilator prazosin vs placebo on exercise duration until marked dyspnea, and on left ventricular function measured by echocardiography, was evaluated in a double-blind, randomized study in 24 patients with chronic left ventricular failure despite digitalis and diuretic therapy. Compared with the double-blind placebo, prazosin reduced resting systolic and diastolic blood pressure and systolic blood pressure times heart rate, improved clinical symptoms, decreased cardiothoracic ratio measured by chest roentgenography, decreased left ventricular and left atrial dimensions, improved ejection fraction and Vcf measured by echocardiography, and improved treadmill exercise duration. All 12 patients taking prazosin had greater than or equal to 20% improved treadmill exercise duration; none of 12 receiving placebo improved. In six of 12 patients taking prazosin, roentgenographic evidence of pulmonary venous congestion disappeared compared with none of the patients on placebo. These data suggest that prazosin may be effective in treating chronic left ventricular failure.

Effect of Sublingual Pentrinitrol on Exercise Tolerance in Angina Pectoris

The effects of 10 mg sublingual pentrinitrol and placebo on the exercise tolerance of 20 patients with angina pectoris were compared. The ten patients who received pentrinitrol had increases in exercise times and metabolic oxygen equivalents (METs) 15 and 60 minutes after administration, whereas no change occurred in ten comparable patients receiving placebo. Pentrinitrol produced lower preexercise systolic blood pressures and systolic blood pressures at point of angina. An increase in heart rate offset the effect of the reduced systolic blood pressure on double product (systolic blood pressure times heart rate). Sublingual pentrinitrol is an effective antianginal drug for at least 60 minutes.

Effect of the vasodilator trimazosin versus placebo on exercise performance in chronic left ventricular failure

The effect of the vasodilator trimazosin versus placebo on exercise duration until marked dyspnea was evaluated in a double blind randomized study in 16 patients with chronic left ventricular failure despite digitalis and diuretic therapy. Trimazosin caused a reduction in resting systolic and diastolic blood pressures and in resting product of systolic blood pressure times heart rate. The improvement in exercise duration from the average of values during the baseline and single blind placebo periods was greater after 3 and 6 weeks of trimazosin therapy (300 and 450 mg daily) after 3 and 6 weeks of double blind placebo therapy ( P < 0.025). Four of eight patients receiving trimazosin had disappearance of pulmonary venous congestion on chest roentgenography compared with none of eight patients receiving placebo. These preliminary data suggest that trimazosin may be effective in treating chronic left ventricular failure.

Effect of smoking marihuana and of a high-nicotine cigarette on angina pectoris.

The purpose of this study was to determine the effect of smoking marihuana and of high-nicotine cigarettes on exercise-induced angina pectoris. Smoking 1 marihuana cigarette increased the resting product of systolic blood pressure times heart rate 54%, increased the venous carboxyhemoglobin level, and decreased the exercise time until angina 50% in 10 patients with angina pectoris. Smoking 1 high-nicotine cigarette increased the resting product of systolic blood pressure times heart rate 36%, increased the venous carboxyhemoglobin level, and decreased the exercise time until angina 23%. Smoking either marihuana or high-nicotine cigarettes decreases exercise performance until angina by increasing myocardial oxygen demand and by decreasing myocardial oxygen delivery. Smoking 1 marihuana cigarette decreased the exercise time until angina more than smoking 1 high-nicotine cigarette (p less than 0.001).

Bypass graft surgery versus medical therapy of angina pectoris

Forty patients with angina pectoris (New York Heart Association functional class III) despite medical therapy were studied. Twenty who underwent coronary bypass graft surgery and 20 comparable patients treated only medically underwent exercise tests during the control period and 3, 6, 9 and 12 months later. One of 20 surgically treated patients (5 percent) died at operation. One year mortality rates were 10 percent (2 of 20 surgically treated patients) and 5 percent (1 of 20 medically treated patients). Three of 20 patients (15 percent) had a myocardial infarction at operation. By 1 year, 4 of 20 surgically treated patients (20 percent) and 1 of 20 medically treated patients (5 percent) had had a myocardial infarction. At 1 year, 18 of 27 grafts (67 percent) were patent. Three and 6 months after the control period, no angina after exercise, a more than 25 percent increase in exercise performance until angina, and an increase in the value for product of systolic blood pressure times heart rate occurred in significantly more surgically than medically treated patients. One year after the control period, 14 of 18 surgically treated patients (78 percent) and 10 of 19 medically treated patients (53 percent) had no angina after exercise or a more than 25 percent increase in exercise performance until angina. One year after the control period, 4 of 16 medical patients (25 percent) and 6 of 15 surgical patients (40 percent) not receiving digitalis had no postexercise ischemic S-T segment depression. These data suggest that the coronary artery bypass operation should be considered only if medical therapy fails to relieve disabling angina.

Effect of freeway travel on angina pectoris.

Ten patients with angina had cardiopulmonary tests done in the control state, after being driven for 90 minutes during heavy morning freeway traffic, and 2 hours after return. The cardiac tests were repeated on a subsequent morning, with the patients breathing compressed, purified air during freeway travel. The expired-air carbon monoxide and arterial carboxyhemoglobin levels significantly increased after breathing freeway air. There was a significant decrease in exercise performance until angina, in systolic blood pressure at angina, in heart rate at angina, in systolic blood pressure times heart rate at angina, and in the FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) after breathing freeway air. Ischemic ST-segment depression occurred in 3 of 10 patients while breathing freeway air. No significant change from control values occurred in the above variables after breathing compressed, purified air. Exposure to heavy freeway traffic increased carboxyhemoglobin levels, causing angina to develop sooner after less cardiac work.

Carboxyhemoglobin caused by smoking nonnicotine cigarettes. Effects in angina pectoris.

The effects of increased carboxyhemoglobin levels caused by smoking nonnicotine cigarettes upon exercise-induced angina were investigated in 10 patients. The mean carboxyhemoglobin level after smoking eight nonnicotine cigarettes, one every 30 minutes, rose from 1.58 to 7.79%. Smoking significantly decreased the mean exercise time from the onset of exercise until the onset of angina from 109.8 to 83.5 seconds. There was significantly less of an increase in systolic blood pressure, heart rate, and product of systolic blood pressure times heart rate after exercise-induced angina after smoking compared to the nonsmoking state. Smoking nonnicotine cigarettes increased the carboxyhemoglobin level, decreasing the rate of oxygen deliverability to the myocardium, with angina developing sooner, following less cardiac work.

The effect of low-nicotine cigarettes on angina pectoris.

Ten subjects with classical exertional angina pectoris were exercised in an upright position with an exercise load of 60 w measured on a bicycle ergometer until the onset of angina pectoris. Exercise was performed four times in a nonsmoking state and four times after smoking a low-nicotine filter cigarette for 5 min. All patients developed angina sooner if they smoked before exercising. The exercise period before angina developed was shortened by an average of 14% after smoking. All subjects developed an increase in the product of systolic blood pressure times heart rate after smoking, indicating an increase in myocardial oxygen consumption. Patients with diseased coronary arteries who exercise after smoking even very low-nicotine cigarettes may be unable to meet the increased demand for myocardial oxygen and may therefore develop angina pectoris sooner.

Observations of the effect of variations in arterial blood pressure: A simple method for continuously recording coronary sinus flow

A sensitive method of recording coronary sinus flow is described which utilizes coronary sinus catheterization, continuously recording the flow with an electromagnetic flowmeter and returning the blood to a femoral vein. Coronary sinus flows in normal dogs were found to have a close linear relationship to mean arterial blood pressure. Coronary sinus flow correlates more closely with the mean arterial blood pressure than with the combined factors of blood pressure times heart rate. The applicability of the method to the study of the effect on coronary flow of various physiologic and pharmacologic factors is demonstrated.

Controlled cardiac output studies in dogs. I. Simple method for estimation of coronary return blood flow in dogs and its evaluation under conditions of controlled cardiac output.

A method lias been presented whereby a semiquantitative estiTiiation of the coronary flow in dogs can be made (within certain experimental limits) by means of a regression equation based on the relationship that coronary flow appears to bear to the product of mean arterial blood pressure times heart rate. The data, from which the regression equation was derived, were obtained by means of the utilization of the "complete right-heart bypass preparation" in seven dogs. The equation for the prediction of coronary return was tested in an additional six dogs, using the "complete right-heart bypass preparation" and the results showed that, if the value for the estimated coronary return were added to the value for caval return, the resultant sum would give a significantly better estimate of the cardiac output than if the value for caval flow only were used as the index.

Myocardial oxygen consumption and coronary blood flow in hypothermia.

Effects of hypothermia (at 32° and 27°C) were determined in the open-chest anesthetized dog prepared for measurement of total coronary flow and myocardial oxygen consumption. When hypothermia was induced at any fixed cardiac output, cardiac oxygen consumption and heart rate declined while blood pressure remained constant. Cardiac external mechanical efficiency increased at the same time. Hypothermia did not alter the relationship between the myocardial oxygen requirement and the total cardiac effort as indicated by the product of blood pressure times heart rate. Without regard to the large individual variability, the coronary venous O2 rose; thus the general trend during the induction of hypothermia was a decline in the coronary A-V oxygen difference, the percentage O2 extracted by the heart and the ratio: cardiac O2 consumption/O2 availability. The coronary venous O2 content and the coronary A-V O2 difference remained fairly constant as the cardiac effort and its oxygen requirement varied during hypothermia, just as in the control period. Thus coronary flow was the only means of adjusting to the altered cardiac oxygen need in both periods.

Role of catecholamines on energetics of the heart and its blood supply.

The effects of continuously infused intravenous l-epinephrine and l-norepinephrine (5 gamma/ kg/min.) were determined in the open-chested anesthetized dog prepared for measurement of total coronary flow and myocardial oxygen consumption. When catecholamines were infused at any fixed cardiac output, cardiac oxygen consumption rose in association with increases in blood pressure and heart rate, while cardiac external mechanical efficiency declined. The significance of the product (blood pressure times heart rate) as an index of the total cardiac effort, as indicated by the myocardial oxygen requirement, is considered in view of the alterations brought about by catecholamines in this relationship. The decline in the coronary A-V oxygen difference, the percentage of oxygen extracted by the heart and the ratio (cardiac oxygen consumption/oxygen availability) and the rise in coronary venous oxygen, are all attributed to a direct action of catecholamines on the coronary vessels. Despite their new levels, the coronary venous oxygen, content and the coronary A-V oxygen difference remain fairly constant as the cardiac effort and its oxygen requirement vary during catecholamine infusion.