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Biomedical subjects

H C Herrmann

Publications and source records attributed to H C Herrmann.

At least 73 records · Page 4Linked to original sources
PubMed1992

Coronary angiography and interventional cardiology.

Percutaneous transluminal coronary angioplasty has become the most commonly applied coronary revascularization procedure. Its growth is due to expanding indications and new patient populations including patients with multivessel coronary artery disease, acute myocardial infarction or cardiogenic shock, and elderly patients. Success rates and complications for percutaneous transluminal coronary angioplasty have remained the same or improved despite the expanding indications and the persistent problem of restenosis. Several recent studies have examined new biologic approaches to restenosis. However, the most exciting area of interventional cardiology continues to be the use and development of new mechanical devices including stents, lasers, and atherectomy for unfavorable anatomic lesions, acute occlusion after angioplasty, and to prevent restenosis. The gold standard in the assessment of coronary disease is still angiography, but newer imaging techniques including intravascular ultrasound and angioscopy have added to our understanding of angioplasty, unstable angina, and the use of new devices.

Angioplasty, Balloon, Coronary↗
PubMed1990

Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure.

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Cardiovascular effects of intracoronary atrial natriuretic peptide administration in man.

An intracoronary drug infusion protocol was employed to assess the hemodynamic effects of synthetic atrial natriuretic peptide in normal subjects and to evaluate its actions on epicardial coronary artery dimensions. Increasing concentrations of synthetic atrial natriuretic peptide (1.75 to 84 micrograms/min) were infused at a constant rate directly into the left coronary artery in eight patients with normal left ventricular function and left coronary artery angiograms. Steady-state hemodynamic parameters and high-fidelity left ventricular pressure were recorded at each dose and indexes of left ventricular contractile and diastolic function were calculated. Coronary angiograms obtained at baseline and the highest dose of atrial natriuretic peptide were compared by quantitative image analysis techniques. At the highest dose administered, atrial natriuretic peptide decreased mean pulmonary artery pressure (-36%, p less than 0.01), pulmonary capillary wedge pressure (-80%, p less than 0.01), left ventricular end-diastolic pressure (-58%, p less than 0.01), left ventricular end-systolic pressure (-11%, p less than 0.01), mean arterial pressure (-8%, p less than 0.05), and pulmonary vascular resistance (-18%, p less than 0.05). Cardiac output and systemic vascular resistance were unchanged, and heart rate and peak positive dP/dt increased. Peak negative dP/dt and the time constant of early diastolic relaxation calculated by the logarithmic method both fell at the highest dose of atrial natriuretic peptide, although the time constants calculated by other less load-sensitive methods were unchanged. Doses of intracoronary atrial peptide that did not alter left ventricular load had no effect on indexes of left ventricular systolic or diastolic function despite a presumably high intramyocardial concentration of the agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Coronary hemodynamic effects of atrial natriuretic peptide in humans.

Studies of the effects of atrial natriuretic peptide on the coronary circulation have yielded conflicting results in animals and have not been fully investigated in human subjects. To further characterize the direct coronary hemodynamic actions of atrial natriuretic peptide in humans and to assess the safety of its administration in patients with coronary artery disease, incremental doses of synthetic atrial natriuretic peptide and nitroglycerin were infused into the left coronary artery in 14 patients, 11 of whom had coronary artery disease. Both agents caused dose-related increases in total coronary sinus blood flow. The largest dose of atrial natriuretic peptide given to all patients (100 micrograms) increased mean coronary sinus blood flow from 127 +/- 7 to 149 +/- 9 ml/min (p less than 0.05) and decreased coronary vascular resistance from 0.93 +/- 0.07 to 0.81 +/- 0.05 mm Hg/ml per min (p less than 0.05); mean arterial blood pressure and heart rate were not affected by this dose of atrial natriuretic peptide. The greatest changes in coronary sinus blood flow (+25%) and coronary vascular resistance (-18%) after atrial natriuretic peptide administration occurred in the patients with coronary artery disease and no other associated cardiovascular disease. The maximal effects of atrial natriuretic peptide were similar to those of nitroglycerin, and no untoward effects were observed. Thus, atrial natriuretic peptide is a direct coronary vasodilator in humans. Its maximal dose effects are similar to those of nitroglycerin and were well tolerated in this small group of patients. The physiologic importance and therapeutic potential of atrial natriuretic peptide in patients with coronary artery disease merit further investigation.

Atrial Natriuretic Factor↗
PubMed1990

Techniques for assessing inotropic effects of drugs in patients with heart failure: application to the evaluation of nicardipine.

Evaluation of new drugs for the treatment of patients with heart failure requires assessment of the inotropic effects of these agents. Use of traditional indexes of contractility has been limited by the confounding effects of load on these measures of contractile function, although they have yielded meaningful conclusions in some studies. Recently, the end-systolic pressure volume relation (ESPVR) has emerged as a relatively load-independent measure of contractility. Because it is difficult to construct the relation in the clinical setting, several approximations have been introduced, some of which have significant limitations. We have applied the ESPVR to the assessment of the inotropic effect of the new dihydropyridine calcium channel blocker, nicardipine, in 15 patients with heart failure caused by systolic dysfunction. We constructed left ventricular pressure-volume loops from micromanometer pressure and radionuclide volume and manipulated afterload with nitroprusside. In response to intravenous nicardipine, mean arterial pressure fell from 91 +/- 4 (mean +/- SEM) to 72 +/- 2 mm Hg, left ventricular end-diastolic pressure fell from 27 +/- 2 to 23 +/- 3 mm Hg, cardiac index increased from 1.7 +/- 0.1 to 2.4 +/- 0.1 L/min/m2, and left ventricular ejection fraction increased from 0.15 +/- 0.01 to 0.19 +/- 0.01 (all p less than 0.05). Heart rate did not change. A rightward shift of the ESPVR, indicating a negative inotropic effect of nicardipine, was observed in 12 of 14 patients (p less than 0.05). We conclude that nicardipine improves left ventricular pump performance despite its negative inotropic effect in patients with severe heart failure. The improvement in pump performance can be attributed to afterload reduction.

Aged↗
PubMed1990

The M-Heart percutaneous balloon mitral Valvuloplasty Registry: initial results and early follow-up. The M-Heart Group.

The initial results, complications and early follow-up of 74 patients undergoing percutaneous balloon mitral valvuloplasty in seven hospitals participating in a multicenter registry are reported. Seventy-four patients with a mean age of 53 years had 75 valvuloplasty procedures performed over a 2.5 year period. Eighty-nine percent of the attempted procedures were completed and resulted in an increase in mean mitral valve area from 1.0 +/- 0.04 to 2.0 +/- 0.1 cm2 (p less than 0.0001); the valve area increased greater than or equal to 50% of the baseline valve area in 73% of the patients. Major complications included procedure-related death (2.7%), cardiac tamponade (6.7%), systemic embolism (2.7%) and emergency surgery (6.7%). At a mean follow-up period of 14.6 months, the condition of the majority of patients had improved, and 89% of 55 patients treated only with valvuloplasty were in New York Heart Association functional class I or II. Thus, hemodynamic and clinical improvement can be obtained in the majority of patients with mitral stenosis treated with balloon valvuloplasty in multiple centers. However, suboptimal results and major complications occurred in a significant number of patients and may limit this procedure to use by experienced operators in hospitals with facilities for cardiac surgery.

Adolescent↗
PubMed1990

Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group.

A multicenter double-blind, randomized, placebo-controlled trial of oral enoximone, a phosphodiesterase inhibitor, was conducted in 102 outpatients (50 receiving enoximone and 52 receiving placebo) with moderate to moderately severe congestive heart failure. All were on a long-term regimen of digoxin and diuretics without vasodilators and converting enzyme inhibitors. Symptom score was obtained, and exercise testing was performed monthly for 4 months. There were no differences between groups in symptoms or exercise duration at the end of 4 months. A subgroup undergoing analysis of oxygen consumption with measurement of anaerobic threshold during exercise showed an increase (p less than 0.05) in anaerobic threshold at 1 month with enoximone. (2.7 +/- 0.8 ml O2/kg/min) compared with placebo (-0.8 +/- 1.2 ml O2/kg/min). This improvement was not sustained at 4 months (0.5 +/- 1.7 ml O2/kg/min with enoximone and 0.2 +/- 1.5 ml O2/kg/min with placebo). The dropout rate was significantly higher (p less than 0.02) with enoximone (46%) than with placebo (25%). Adverse effects other than death were slightly, but not significantly, higher with enoximone (32%) than with placebo (22%). During therapy, five deaths occurred in the enoximone group, and none occurred in the placebo group (p less than 0.05). Two deaths were sudden, two were from progressive congestive heart failure, and one was from acute myocardial infarction. With intention-to-treat analysis and inclusion of patients who were removed from therapy because of lack of study drug effect, 10 deaths occurred in the enoximone group, and three occurred in the placebo group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features.

The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, -0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning).

Adaptation, Physiological↗
PubMed1989

Percutaneous aortic balloon valvuloplasty in octogenarians: morbidity and mortality.

STUDY OBJECTIVE: To examine the morbidity, mortality, and hospital course of an elderly patient sample (mean age, 86 years; 95% CI, 84 to 87) having percutaneous aortic balloon valvuloplasty. DESIGN: Retrospective consecutive case series before and after balloon valvuloplasty. SETTING: Tertiary care referral hospital. PATIENTS: Consecutive sample of 26 patients aged 80 years or older with symptomatic aortic stenosis referred for balloon valvuloplasty from July 1987 to July 1988. MEASUREMENTS AND MAIN RESULTS: Percutaneous aortic balloon valvuloplasty reduced the transvalvular gradient from 59 (95% CI, 51 to 67) to 31 mm Hg (95% CI, 26 to 35; P less than 0.0001) and increased aortic valve area from 0.45 (95% CI, 0.38 to 0.51) to 0.67 cm2 (95% CI, 0.58 to 0.76; P less than 0.0001). The mean length of hospital stay for the entire study population was 11.2 days (95% CI, 7.3 to 15.2) at a total hospital charge per patient of $29,600 (95% CI, 21,050 to 38,150). For patients having procedural complications (11 complications in 8 patients), surgical procedures, or cardiogenic shock, the mean hospital stay increased to 16.2 days (95% CI, 6.2 to 26.2; P less than 0.05) and the hospital charge increased to $44,400 (95% CI, 24,280 to 64,520; P less than 0.01). Two patients who presented with cardiogenic shock died, and 1 patient had an aortic valve replacement before discharge. Four patients were recently discharged (less than 1 month) and follow-up was obtained in the remaining 19 patients at 6.1 months (95% CI, 4.1 to 8.1). Five more patients, including the remaining patient who presented with cardiogenic shock, died after discharge for an overall mortality of 32%. Twelve of the remaining fourteen patients had fewer symptoms and improved an average of 1.1 New York Heart Association classes (95% CI, 0.7 to 1.4; P less than 0.0001). CONCLUSIONS: Percutaneous aortic balloon valvuloplasty in patients 80 years and older improves hemodynamics and symptoms of heart failure during short-term follow-up in most patients, but overall mortality is high in this elderly patient population. Hospital charges and length of stay were much higher in patients with complications or coexisting medical illnesses. Valvuloplasty is a reasonable alternative treatment for patients with aortic stenosis who require palliative treatment of symptoms and have high surgical risk.

Aged↗
PubMed1989

Single large-balloon percutaneous mitral valvuloplasty.

Successful percutaneous balloon mitral valvuloplasty was performed in six patients utilizing single large (up to 30 mm diameter) balloons. Mitral valve area increased from 1.1 +/- 0.1 to 2.5 +/- 0.3 cm2 (P less than 0.01), and there were no complications or significant increases in mitral regurgitation. Single large-balloon mitral valvuloplasty may be as effective as the currently used double-balloon technique and may allow the procedure to be performed more easily and quickly.

Adult↗
PubMed1989

Linearity of the left ventricular end-systolic pressure-volume relation in patients with severe heart failure.

The left ventricular end-systolic pressure-volume relation is a relatively load-independent measure of left ventricular contractile function. Linearity of the relation derived from full left ventricular pressure-volume loops has not previously been demonstrated for patients with severe heart failure. Therefore, nine patients with markedly depressed left ventricular systolic function (ejection fraction 0.14 +/- 0.08) were studied with micromanometer left ventricular pressure measurement and simultaneous radionuclide ventriculography. Afterload was reduced with graded infusions of nitroprusside, allowing construction of pressure-volume loops under four afterload conditions in four patients and three afterload conditions in the other five patients. The end-systolic pressure-volume relation derived from the pressure-volume loops was found to be linear for the range of pressures and volumes examined, with correlation coefficients in individual patients ranging from 0.936 to 0.999 (mean 0.981). The mean slope of the relation (or end-systolic elastance) was 0.71 mm Hg/ml (range 0.42 to 1.52), and the extrapolated volume intercept at zero pressure was positive in all patients. An exponential relation between end-systolic elastance and ejection fraction was demonstrated for this group of patients. Approximations of end-systolic elastance obtained from measurements other than the full pressure-volume loops correlated variably with "true" elastance obtained from the pressure-volume loops. The relation between stroke work and end-diastolic volume was nonlinear in most patients. Thus, the end-systolic pressure-volume relation is linear in the "physiologic" range in patients with severe heart failure. This finding should permit construction of the relation from two loading conditions in clinical studies, facilitating its use as an index of contractile function in patients with heart failure.

Aged↗
PubMed1988

Effects of atrial natriuretic factor on coronary hemodynamics and myocardial energetics in patients with heart failure.

Synthetic analogues of atrial natriuretic factor (ANF) have been developed for potential use as therapeutic agents in the treatment of congestive heart failure and hypertension. We studied the effects of 14 intravenous infusions of synthetic ANF (anaritide, human ANF 102-126) on coronary hemodynamics and myocardial energetics in six patients with heart failure. ANF infusion caused no change in coronary blood flow and a fall in coronary vascular resistance from 1.22 +/- 0.22 to 1.08 +/- 0.18 mm Hg-min/ml (p less than 0.05). Myocardial oxygen and lactate consumption were unchanged from baseline values. Mean arterial pressure fell from 91 +/- 4 to 78 +/- 3 mm Hg (p less than 0.01), right atrial pressure fell from 10 +/- 1 to 8 +/- 1 mm Hg (p less than 0.01), pulmonary capillary wedge pressure fell from 21 +/- 3 to 16 +/- 2 mm Hg (p less than 0.01), heart rate and cardiac index were unchanged, and systemic vascular resistance fell from 1346 +/- 130 to 1087 +/- 98 dyne-sec/cm5 (p less than 0.05). We conclude that infusion of ANF in hemodynamically effective doses in patients with heart failure decreases coronary vascular resistance with no change in coronary blood flow or myocardial oxygen or lactate metabolism.

Atrial Natriuretic Factor↗
PubMed1988

Percutaneous balloon mitral valvotomy for patients with mitral stenosis. Analysis of factors influencing early results.

Percutaneous balloon mitral valvotomy has recently been developed as an alternative to surgical commissurotomy for patients with rheumatic mitral stenosis. We analyzed our initial experience with 60 consecutive procedures performed in 49 patients over 1 1/2 years and identified factors influencing the immediate hemodynamic results. For the total patient population, the mitral valve area increased after percutaneous mitral valvotomy from 0.8 +/- 0.04 to 1.6 +/- 0.11 cm2 (p less than 0.001). Mean diastolic mitral gradient fell from 18 +/- 1 to 7 +/- 0.4 mm Hg (p less than 0.001), and cardiac output increased from 3.8 +/- 0.2 to 4.5 +/- 0.2 L/min (p less than 0.01). Although percutaneous mitral valvotomy resulted in an increase in mitral valve area in each patient, a suboptimal result, as defined by a postprocedure mitral valve area of 1.0 cm2 or less, an increase in area of 25% or less, or a final mitral gradient of 10 mm Hg or more occurred in 21 of the 60 procedures (35%). Multivariate analysis of 16 variables was performed to determine which factors might predict this result. Patients with a suboptimal result were more likely to have severe valve leaflet thickening or immobility and an extreme degree of subvalvular thickening and calcification on echocardiogram. Other factors that predicted a suboptimal result were a smaller effective balloon dilating area and the presence of atrial fibrillation. Thus optimal immediate hemodynamic results can be obtained in the majority of patients undergoing percutaneous mitral valvotomy. Optimal results may be expected in patients in normal sinus rhythm, with pliable mitral leaflets, and with no severe subvalvular disease identified by echocardiography, who undergo dilation with large effective balloon dilating areas.

Catheterization↗
PubMed1987

Preload dependence of Doppler-derived indexes of left ventricular diastolic function in humans.

To determine the effect of filling pressure on the pattern of left ventricular filling in humans, the mitral flow velocity profile was measured by pulsed wave Doppler echocardiography during right and left heart catheterization in 11 patients before and during nitroglycerin infusion. Nitroglycerin reduced mean arterial pressure from 90 +/- 9 to 80 +/- 11 mm Hg (p less than 0.001) and mean pulmonary capillary wedge pressure from 9 +/- 4 to 4 +/- 2 mm Hg (p less than 0.001). Cardiac output fell from 6.6 +/- 1.5 to 5.5 +/- 1.4 liters/min (p less than 0.001) and heart rate increased from 60 +/- 13 to 65 +/- 14 beats/min (p less than 0.002). The time constant of isovolumic relaxation (TI.) decreased from 51 +/- 9 to 46 +/- 8 ms (p less than 0.01), indicating faster left ventricular relaxation. Nitroglycerin altered the Doppler characteristics of the early filling (E) wave but not those of the atrial contraction (A) wave. Peak velocity of the E wave decreased from 56 +/- 14 to 44 +/- 9 cm/s (p less than 0.001), peak velocity of the A wave did not change and the ratio of peak velocities of the E and A waves decreased from 0.97 +/- 0.33 to 0.77 +/- 0.20 (p less than 0.02). The deceleration of the E wave decreased from 289 +/- 138 to 186 +/- 71 cm/s2 (p less than 0.02). The ratio of velocity-time integral of the A wave to total velocity-time integral (that is, contribution of atrial contraction to total filling) increased from 0.31 +/- 0.09 to 0.36 +/- 0.08 (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Inotropic effect of enoximone in patients with severe heart failure: demonstration by left ventricular end-systolic pressure-volume analysis.

Left ventricular end-systolic pressure-volume analysis was employed to assess the inotropic effect of the phosphodiesterase inhibitor enoximone (formerly MDL-17,043) in nine patients with severe heart failure (New York Heart Association class IV symptoms, mean ejection fraction = 0.22). Left ventricular pressure-volume loops were constructed using high fidelity left ventricular pressure measured with micromanometer-tipped catheters and simultaneous left ventricular volume obtained by gated blood pool imaging. Afterload was reduced with the vasodilator nitroprusside to generate the baseline left ventricular end-systolic pressure-volume relation, a relatively load-independent measure of contractile function. The intravenous administration of enoximone (mean dose 75 mg) shifted the end-systolic pressure-volume point upward and leftward from the baseline pressure-volume relation in eight of the nine patients, demonstrating a positive inotropic effect of this agent. The maximal rate of left ventricular pressure development (peak positive dP/dt) increased from 1,030 +/- 142 to 1,381 +/- 219 mm Hg/s (p less than 0.01) on enoximone despite a significant decrease in preload (as assessed by left ventricular end-diastolic pressure and volume) and a small, insignificant decrease in mean arterial pressure. Two patients developed angina after enoximone administration; both patients had coronary artery disease and experienced a greater than 30% increase in heart rate-systolic blood pressure product. Thus, enoximone has a significant inotropic effect in patients with severe heart failure. Like other inotropic drugs, it has the potential to increase myocardial oxygen demand and thereby precipitate ischemia.

Blood Pressure↗
PubMed1987

Diastolic function in patients with severe heart failure: comparison of the effects of enoximone and nitroprusside.

To assess whether the phosphodiesterase inhibitor enoximone has a specific, direct effect on left ventricular diastolic function distinct from its inotropic and vasodilator actions, we compared the effects of enoximone and the pure vasodilator nitroprusside in 11 patients with severe heart failure. Mean (+/- SEM) left ventricular ejection fraction was 0.20 +/- 0.03. Simultaneous left ventricular pressure and radionuclide angiographic volume were obtained at baseline, during infusion of nitroprusside, and after intravenous administration of enoximone. Left ventricular end-diastolic pressure (LVEDP) and volume (LVEDV) decreased with both agents (p less than .01 vs control); LVEDP was lower for nitroprusside than for enoximone (p less than .01) despite a similar LVEDV. Nitroprusside decreased the time constant of exponential left ventricular pressure decay, TL (measured by the logarithmic method), from 84 +/- 10 to 65 +/- 8 msec (p less than .01) but had no significant effect on TD (measured by the derivative method), maximum negative dP/dt, or the peak rate of early diastolic filling. Enoximone shortened TL from 86 +/- 12 to 61 +/- 9 msec (p less than .01) and increased maximum negative dP/dt from 897 +/- 101 to 1135 +/- 134 mm Hg/sec (p less than .01) but did not affect TD or the peak filling rate. The left ventricular diastolic pressure-volume relation was shifted downward in only three of 11 patients on nitroprusside and three of 11 patients on enoximone, and these shifts were attenuated by adjusting for simultaneous changes in right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Diastole↗