Changes In Stroke Work Research Articles

Non-invasive pressure-volume analysis by 3-dimensional echocardiography: a novel method for left ventricular stroke work estimation

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Institute for Surgical Research, Oslo University Hospital. Introduction Left ventricular pressure-volume analysis is a powerful method to quantify left ventricular function. A major limitation of its clinical utility, however, is the need for invasive pressure and volume measurements. We hypothesized that accurate non-invasive left ventricular (LV) stroke work analysis is feasible by combining continuous 3-dimensional (3D) echocardiographic LV volume measurements with non-invasive LV pressure curve estimation. Purpose To investigate if LV stroke work can be estimated non-invasively by combining 3D echocardiographic volume measurements with non-invasive pressure curve estimation. Methods In 21 open-chest anesthetized canines, piezoelectric crystals were placed in the LV subendocardium for volume measurements and a micromanometer catheter was placed in the LV cavity for pressure measurements. Echocardiography was performed directly on the heart to acquire 3D LV volumes and timings of mitral and aortic valve events. The estimated LV pressure curve was obtained by adjusting the cardiac phases of an LV reference pressure curve to these valve events and adjusting its amplitude to measured peak LV pressure. Stroke work was calculated as the area under the pressure-volume curve from mitral valve closure to mitral valve opening. Non-invasively estimated and invasively measured stroke work were compared. Recordings were done during baseline, aortic constriction, dobutamine infusion and after induction of left bundle branch block by ablation. Results Panel A in the Figure illustrates non-invasive (left) and invasive (right) pressure-volume loops from a representative experiment. Baseline and the different interventions are colour-coded allowing visual comparison of the similar non-invasive and invasive stroke work. Panel B shows the pooled data from all experiments. There was a strong correlation (r=0.98, p<0.0001) and good agreement between the non-invasive and invasive stroke work. Furthermore, the non-invasive method captured similar changes in stroke work during interventions as compared to the invasive method (Panel C). Conclusions Non-invasive pressure-volume analysis by combining 3D echocardiography and estimated pressure for stroke work evaluation, is feasible and accurate.

Abstract 12821: Progressive Improvement in Left Ventricular Performance Associated With Progressive Regional Dyssynchrony

Background : We have shown that non-excitatory epicardial stimulation (NES) increases measures of cardiac function mediated by local release of norepinephrine. In this further investigation we determined whether NES is accompanied by improved indices of left ventricular (LV) performance, reflected in PV loops and timing of aortic valve opening and closing. Methods : Anesthetized pigs (n=6) were instrumented with a LV high-fidelity pressure/volume conductance transducer, thoracic aortic pressure transducer, left atrial (LA)/ LV epicardial electrodes, and sonomicrometer segment length (SL) gauges placed proximal (lateral base) and distal (posterior mid LV) to the LV stimulation site. During constant LA pacing, LV pulses (0.8ms, 2-3x threshold volts) were applied during the absolute refractory period for 3 minutes (3x), before and after β-receptor blockade (BB, metoprolol). Data were analyzed at baseline, and at an estimated 30%, 60% and 100% of developed ventricular dyssynchrony (DVD) contraction pattern. Results: Consistent with earlier findings, NES resulted in an early shortening and relaxation pattern of the proximal SL manifest as an 80% decrease in the LVP vs. SL loop area in the absence of change in the remote segment. This was accompanied by an increase in peak systolic pressure and LV dP/dt max. Although NES did not change the area of the LVP vs. LV volume loop (stroke work) or alter the interval from LV electrical activation (R wave) to the onset of LV pressure increase, aortic valve opening occurred up to 14.1 ± 2.8 ms earlier (p <0.01) compared to baseline. The duration of an open aortic valve slightly increased (6.0 ± 3.9 ms) whereas ejection duration from valve opening to peak Pao decreased 18.2 ± 3.0 ms (p < 0.01). Conclusion : These findings demonstrate that NES elicits a local contractile dysynchrony resulting in an enhanced cardiac inotropic state characterized by more rapid global LV contraction with earlier aortic valve opening with no change in stroke work.

Invasive Real Time Biventricular Pressure-Volume Loops to Monitor Dynamic Changes in Cardiac Mechanoenergetics During Structural Heart Interventions: Design and Rationale of a Prospective Single-Center Study

BackgroundTranscatheter valvular interventions affect cardiac and hemodynamic physiology by changing ventricular (un-)loading and metabolic demand as reflected by cardiac mechanoenergetics. Real-time quantifications of these changes are scarce. Pressure-volume loop (PVL) monitoring appraises both load-dependent and load-independent compounds of cardiac physiology including myocardial work, ventricular unloading, and ventricular-vascular interactions. The primary objective is to describe changes in physiology induced by transcatheter valvular interventions using periprocedural invasive biventricular PVL monitoring. The study hypothesizes transcatheter valve interventions modify cardiac mechanoenergetics that translate into improved functional status at 1-month and 1-year follow-up. MethodsIn this single-center prospective study, invasive PVL analysis is performed in patients undergoing transcatheter aortic valve replacement or tricuspid or mitral transcatheter edge-to-edge repair. Clinical follow-up is per standard of care at 1 and 12 months. This study aims to include 75 transcatheter aortic valve replacement patients and 41 patients in both transcatheter edge-to-edge repair cohorts. ResultsThe primary outcome is the periprocedural change in stroke work, potential energy, and pressure-volume area (mmHg mL−1). The secondary outcomes comprise changes in a myriad of parameters obtained by PVL measurements, including ventricular volumes and pressures and the end-systolic elastance—effective arterial elastance ratio as a reflection of ventricular—vascular coupling. A secondary endpoint associates these periprocedural changes in cardiac mechanoenergetics with functional status at 1 month and 1 year. ConclusionsThis prospective study aims to elucidate the fundamental changes in cardiac and hemodynamic physiology during contemporary transcatheter valvular interventions.

Baroreceptor Unloading at Rest and During Exercise in Heart Failure Exacerbates Ventricular‐Vascular Coupling

The arterial baroreflex is the primary reflex controlling arterial blood pressure on a beat-by-beat basis via modulation of autonomic output to change cardiac output and systemic vascular resistance. This moment-to-moment control of arterial pressure is well maintained with the transition from rest to exercise. However, in systolic heart failure (HF) baroreflex dysfunction can occur. Effective control of cardiac output occurs in part via efficient energy transfer from the left ventricle to the systemic circulation; known as ventricular-vascular coupling. Ventricular-vascular coupling can be evaluated by changes in stroke work and the relationship between effective arterial elastance to left ventricular maximal elastance. We investigated if the effects of baroreceptor unloading (via bilateral carotid occlusion) on effective arterial elastance and stroke work at rest, and during exercise were altered in HF, in conscious chronically instrumented canines. We hypothesized that in healthy subjects the baroreflex maintains ventricular-vascular coupling whereas in HF, exacerbated increases in effective arterial elastance as a result of baroreceptor unloading would cause decoupling of the ventricular-vascular interaction. We observed in healthy subjects that baroreceptor unloading significantly increased effective arterial elastance (Ea) and stroke work (SW) at rest (Ea: +1.6 ± 0.2 mmHg/ml) (SW: +1.8 ± 0.1 L/mmHg) and during exercise (Ea: +1.4 ± 0.2 mmHg/ml) (SW: +1.6 ± 0.2 L/mmHg) thus maintaining ventricular-vascular coupling. In HF, ventricular-vascular uncoupling is already apparent with higher effective arterial elastance and reduced maximal ventricular elastance. Baroreceptor unloading in HF further worsens ventricular-vascular coupling at rest and during exercise by eliciting ~2-3 fold increases in effective arterial elastance (EaΔREST +4.3 ± 0.3 mmHg/ml) (EaΔEX +2.5 ± 0.5 mmHg/ml) unaccompanied by much improvement in stroke work (SWΔREST +0.1 ± 0.5 L/mmHg) (SWΔEX +0.5 ± 0.1 L/mmHg). We conclude that the ability of the arterial baroreflex to raise cardiac output in heart failure is impaired in part due to further reflex induced uncoupling of the ventricular-vascular relationship. This likely contributes to impaired reflex control of arterial pressure during hypotensive challenges in HF.

Atrioventricular optimization in cardiac resynchronization therapy with quadripolar leads: should we optimize every pacing configuration including multi-point pacing?

This study aims to define an atrioventricular (AV) delay optimization method for cardiac resynchronization therapy (CRT) with a quadripolar left ventricular (LV) lead based on intrinsic conduction intervals. Heart failure patients with a left bundle branch block underwent CRT implantation with a quadripolar LV lead. Invasive LV pressure-volume loops were recorded during four biventricular and three multi-point pacing (MPP) settings, using four patient-specific paced AV delays. Haemodynamic response was defined as change in stroke work (Δ%SW) compared to intrinsic rhythm and was related to the following conduction intervals: right atrial pacing to right ventricular sensing interval (RAp-RVs), Q to LV sensing interval normalized to QRS duration (QLV/QRSd), PR-interval, and P-wave duration. In 44 patients, the largest Δ%SW (104 ± 76%) occurred at a paced AV delay of 128 ± 32 ms, at 47 ± 9% of RAp-RVs. Optimal AV delay of biventricular pacing (126 ± 26 ms) did not differ from MPP (126 ± 21 ms, P = 0.29). Intra-class correlation coefficient between optimal AV delays of different pacing configurations was 0.64 (0.45-0.78, P < 0.001). Although not statistically significant, Δ%SW at 50% of RAp-RVs (98 ± 74%) was closer to the maximal achievable Δ%SW increase than a fixed interval of 120 ms (96 ± 73%, P = 0.60). RAp-RVs, QLV/QRSd, PR interval, and P-wave duration were associated with the optimal AV delay in univariate analysis, but only RAp-RVs remained significantly associated in multivariate analysis (R = 0.69). The AV delay that provides highest haemodynamic response is similar for various LV pacing configurations and for MPP. An AV delay ∼50% of RAp-RVs creates an acute haemodynamic response close to the maximal patient-specific response.

Pressure-Volume Loop Analysis of Multipoint Pacing With a Quadripolar LeftVentricular Lead in Cardiac Resynchronization Therapy.

This study aimed to compare multipoint pacing (MPP) to optimal biventricular pacing with a quadripolar left ventricular (LV) lead and find factors associated with hemodynamic response to MPP. MPP with a quadripolar LV lead may increase response to cardiac resynchronization therapy. Heart failure patients with a left bundle branch block underwent cardiac resynchronization therapy implantation. Q to LV sensing interval divided by the intrinsic QRS duration was measured. Invasive pressure-volume loops were assessed during 4 biventricular pacing settings and 3 MPP settings, using 4 atrioventricular delays. Hemodynamic response was defined as change in stroke work (Δ%SW) compared with baseline measurements during intrinsic conduction. Δ%SW of MPP was compared with conventional biventricular pacing using the distal electrode and the electrode with highest Δ%SW (BIV-OPT). Forty-three patients were analyzed (age 66 ± 10 years, 63% men, 30% ischemic cardiomyopathy, LV ejection fraction 29 ± 8%, and QRS duration 175 ± 13 ms). Q to local LV sensing interval corrected for QRS duration was 84 ± 8%, and variation between LV electrodes was 9 ± 5%. Compared with conventional biventricular pacing using the distal electrode, MPP showed a significant higher increase of SW (Δ%SW+15 ± 35%; p< 0.05) with a large interindividual variation. There was no significant difference in Δ%SW with MPP compared with BIV-OPT (-5 ± 24%; p= 0.19). Male sex and low LV ejection fraction were associated with increase in Δ%SW due to MPP versus BIV-OPT in multivariate analysis, while ischemic cardiomyopathy was only associated in univariate analysis. Optimization of the pacing site of a quadripolar LV lead is more important than to program MPP. However, specific subgroups (i.e., especially men) may benefit substantially from MPP.

Can We Use the Intrinsic Left Ventricular Delay (QLV) to Optimize the Pacing Configuration for Cardiac Resynchronization Therapy With a Quadripolar Left Ventricular Lead?

Previous studies indicated the importance of the intrinsic left ventricular (LV) electric delay (QLV) for optimal benefit to cardiac resynchronization therapy. We investigated the use of QLV for achieving optimal acute hemodynamic response to cardiac resynchronization therapy with a quadripolar LV lead. Forty-eight heart failure patients with a left bundle branch block were prospectively enrolled (31 men; age, 66±10 years; LV ejection fraction, 28±8%; QRS duration, 176±14 ms). Immediately after cardiac resynchronization therapy implantation, invasive LV pressure-volume loops were recorded during biventricular pacing with each separate electrode at 4 atrioventricular delays. Acute cardiac resynchronization therapy response, measured as change in stroke work (Δ%SW) compared with intrinsic conduction, was related to intrinsic interval between Q on the ECG and LV sensing delay (QLV), normalized for QRS duration (QLV/QRSd), and electrode position. QLV/QRSd was 84±9% and variation between the 4 electrodes 9±5%. Δ%SW was 89±64% and varied by 39±36% between the electrodes. In univariate analysis, an anterolateral or lateral electrode position and a high QLV/QRSd had a significant association with a large Δ%SW (all P <0.01). In a combined model, only QLV/QRSd remained significantly associated with Δ%SW (P<0.05). However, a direct relation between QLV/QRSd and Δ%SW was only seen in 24 patients, whereas 24 patients showed an inverse relation. The large variation in acute hemodynamic response indicates that the choice of the stimulated electrode on a quadripolar lead is important. Although QLV/QRSd was associated with acute hemodynamic response at group level, it cannot be used to select the optimal electrode in the individual patient.

Beat-by-Beat Estimation of the Left Ventricular Pressure-Volume Loop Under Clinical Conditions.

This paper develops a method for the minimally invasive, beat-by-beat estimation of the left ventricular pressure-volume loop. This method estimates the left ventricular pressure and volume waveforms that make up the pressure-volume loop using clinically available inputs supported by a short, baseline echocardiography reading. Validation was performed across 142,169 heartbeats of data from 11 Piétrain pigs subject to two distinct protocols encompassing sepsis, dobutamine administration and clinical interventions. The method effectively located pressure-volume loops, with low overall median errors in end-diastolic volume of 8.6%, end-systolic volume of 17.3%, systolic pressure of 19.4% and diastolic pressure of 6.5%. The method further demonstrated a low overall mean error of 23.2% predicting resulting stroke work, and high correlation coefficients along with a high percentage of trend compass 'in band' performance tracking changes in stroke work as patient condition varied. This set of results forms a body of evidence for the potential clinical utility of the method. While further validation in humans is required, the method has the potential to aid in clinical decision making across a range of clinical interventions and disease state disturbances by providing real-time, beat-to-beat, patient specific information at the intensive care unit bedside without requiring additional invasive instrumentation.

Abstract 18500: Determinants of Cardiac Loading During Long Duration Spaceflight

INTRODUCTION: Prolonged exposure to microgravity (bedrest) leads to a decrease in cardiac mass by ~1%/week due to reduced cardiac work. However, the magnitude of reduction with long duration spaceflight with modern countermeasures is unknown. One purpose of this study (Integrated CardioVascular) is to quantify cardiac work and mass in astronauts during 6 months on the International Space Station (ISS). METHODS: Data from 5 astronauts who completed a long duration stay on the ISS (~6 months) were analyzed. Cardiac mass (MRI) was measured pre- and post-flight. Continuous finger blood pressure waveforms (Volume-Clamp) for 24 hours were measured before and the end of flight (15 days before they returned to the earth). Cardiac mass was estimated by (epicardial volume - endocardial volume)*1.05 g/mL. Daily stroke work and cardiac work were calculated by the sum of each stroke volume (ΣSV, SV; stroke voluem) and stroke work (ΣSV*cmBPs, cmBPs; mean central blood pressure during systole) per day, respectively. The central blood pressure waveform was mathematically reconstructed from the finger blood pressure waveform. Beat-to-beat SV was estimated with BP waveform analysis (Modelflow). RESULTS: The %change in cardiac mass was variable (+1% on average) with divergent responses among astronauts (-4%~ +14%). All astronauts showed the reduction of cardiac work (-15±9%), while 4 of 5 showed the reduction of stroke work (-8±12%). A strong positive linear relationship was shown between % changes in cardiac work vs. mass (R 2 =0.471) as well as %changes in stroke work vs. cardiac mass (R 2 =0.905). CONCLUSIONS: Cardiac atrophy during long duration spaceflight is highly dependent on the relative changes in cardiac work and stroke work from preflight to the end of the mission. Current countermeasures may be protective in some, but not all astronauts.

Latent left ventricular dysfunction in patients with mitral regurgitation: Feasibility of measuring diminished contractile reserve from a simplified model of noninvasively derived left ventricular pressure-volume loops

Background Assessment of left ventricular (LV) contractility in mitral regurgitation is difficult, and latent systolic dysfunction may be present despite conventional indexes being in the “normal” range. We sought to demonstrate the presence of latent LV dysfunction in mitral regurgitation by showing diminished contractile reserve with the use of simplified pressure-volume loops from noninvasively derived parameters. Methods and Results We performed exercise echocardiography in 72 patients with isolated mitral regurgitation, minimal or no symptoms, normal resting LV function, and no coronary disease who subsequently underwent uncomplicated valve repair and in 15 healthy subjects. Simplified pressure-volume loops were constructed and LV stroke work was estimated at rest and immediately after exercise. As pressures were estimated, the findings were confirmed with a validated numerical model to estimate stroke work in patients and control subjects. Patients had a higher stroke work than did control subjects at rest (1.45 ± 0.39 vs 0.92 ± 0.21 J, P < .001). Eighteen patients had LV dysfunction develop after surgery. Patients with postrepair dysfunction had a significantly lower exercise stroke work (1.79 ± 0.69) than did patients without (2.28 ± 0.84 J, P = .02), but there was no difference in resting stroke work (1.48 ± 0.39 vs 1.44 ± 0.4, P = not significant). Change in stroke work with exercise was higher in patients with normal postoperative function (0.84 ± 0.59 J) and control subjects (0.59 ± 0.36 J) than patients with postoperative dysfunction (0.31 ± 0.55 J, P = .001). The numerical model confirmed the lower exercise stroke work and change in stroke work in patients with postoperative dysfunction. Conclusions The clinical study and numerical model confirmed diminished contractile reserve in patients who had LV dysfunction develop after uncomplicated mitral valve repair. Diminished contractile reserve may be a preoperative marker of latent contractile dysfunction. (Am Heart J 1999;137:427-34.)

Sodium bicarbonate versus carbicarb in canine myocardial hypercarbic acidosis

The objective of this study was to compare the in vivo effects of sodium bicarbonate (NaHCO 3) and Carbicarb infusion on regional contractile performance and acid-base status in the setting of hypercarbic acidosis. Animals (N = 9) were anesthetized and paralyzed using sodium pentothal, halothane, and pancuronium bromide, and mechanically ventilated with an air-O 2 mixture so that arterial Po 2 was ≥300 mm Hg. Following beta-adrenergic blockade, alveolar ventilation was gradually reduced over a 50-minute period to increase arterial Pco 2 to 60 to 80 mm Hg. Each of the following solutions was then infused in consecutive order directly into the left anterior descending artery coronary artery for 15 minutes: (1) 8.4% NaHCO 3 at 2 mL/min; (2) 5% sodium chloride at 2 mL/min, equivalent to NaHCO 3 in osmolality; (3) 6.3% Carbicarb at 0.5 mL/min, equivalent to NaHCO 3 in buffer capacity; and (4) 6.3% Carbicarb at 2 mL/min, equivalent to NaHCO 3 in volume. Regional stroke work analog (ultrasonic dimension transducers), interstitial myocardial pH (Khuri electrode), coronary blood flow (doppler flow probe), and hemodynamic/metabolic variables (heart rate, blood pressure, arterial and coronary venous blood gases) were measured at 1, 5, 10, and 15 minutes during each infusion and 10 minutes after the infusion was discontinued, ie, at 25 minutes. Animals were allowed to recover for 45 minutes between interventions. Values at each time point were compared with baseline for statistical significance. Small reductions in interstitial myocardial pH ( P < .05) and stroke work ( P > .05) were observed within 1 minute of NaNCO 3 administration. Both parameters increased significantly from baseline levels thereafter, ie, interstitial myocardial pH at 5 minutes and stroke work at 15 minutes. Infusion of Carbicarb invariably was associated with an increase ( P < .05) in interstitial myocardial pH. Stroke work increased ( P < .05) during low-dose Carbicarb administration, but infusion of the higher dose was accompanied by a biphasic response, ie, an increase ( P < .05) from 0 to 5 minutes, followed by a gradual decrease that achieved statistical significance 10 minutes after termination of the infusion. End-diastolic length was inversely proportional to changes in stroke work, and coronary blood flow varied directly with changes in coronary venous Pco 2. Myocardial O 2 consumption decreased ( P < .05) during Carbicarb infusion, but changes during NaHCO 3 did not reach statistical significance. Our findings lend support to the hypothesis that intramyocardial pH determines myocardial function independent of CO 2 production by buffer therapy. While Carbicarb may restore intramyocardial pH and improve myocardial function more rapidly than NaHCO 3, both buffers neutralize the effects of intracellular acidosis to a similar extent when they enter the myocardium. Our results do not support the argument that NaHCO 3 is detrimental to myocardial contractile function when spontaneous contractile function is present.

Beat-to-beat regulation of left ventricular function in the intact cardiovascular system.

A variety of regulatory mechanisms have evolved to control the heart's pump function because the cardiovascular system must continually adapt to the changing demands that body functions place on it. This regulation takes place through many physiological systems; however, fine adjustments in cardiac pumping probably require adaptations more quickly than external control mechanisms (such as the autonomic nervous system) can compensate. Thus cardiac pumping is also regulated by mechanisms intrinsic to the heart. To better understand these intrinsic control mechanisms, we studied the beat-to-beat response of left ventricular function to continually varying changes in loading conditions produced by transiently occluding the pulmonary artery, venae cavae, and aorta. We used multiple linear regression to identify and quantify the important beat-to-beat determinants of left ventricular systolic function, quantified as stroke work. We could not adequately explain or predict beat-to-beat changes in stroke work with traditional determinants of ventricular function, preload, afterload, and heart rate, because a large systematic error remains after taking these traditional determinants of function into account. To eliminate this systematic error, we had to include some function of previous beat stroke volume and end-systolic size and pressure. This additional information significantly improved both our ability to model the observed transient changes in left ventricular stroke work and to predict additional observations that were not used to develop our model. We conclude that previous beat contraction history is an important determinant of left ventricular function and implies an important regulatory mechanism whereby the left ventricle can fine tune its function from beat to beat in response to continually changing loading conditions.

Significance of left ventricular power waveform on changes in stroke work during pulsatile left ventricular bypass

The object of this paper is to introduce the “peakedness” of the left ventricular power waveform as an index of the effectiveness of the pulsatile ventricular bypass (LVBP). The “peakedness” is determined by the position of the peak and the rate of ascent and decline of the instantaneous left ventricular power waveform. In eight open-chested dogs with coronary artery ligation, it has been found that the “peakedness” of the LV power waveform during assistance is important in determining the efficacy of LVBP. When the LV power waveform, the instantaneous product of LV pressure and aortic flow, has a broad width about the peak with an early rise to peak (low value of “peakedness” factor), the chance of improvement in stroke work after bypass is greater than when the waveform is sharply peaked with a delayed rise (high value of “peakedness”). Improvement in stroke work (SW) occurred when the percentage bypass flow was between 45 and 60%. Among the pumping runs with improved SW and CO, there was no consistent relationship between the percentage changes in SW and CO and the percentage bypass flow. The data suggest that “peakedness” may be of importance, because it evaluated the effect of left ventricular bypass on the performance of the native ventricle during postischemic periods.

Variability in response to norepinephrine in acute myocardial infarction

Twenty-seven patients with acute myocardial infarction were studied by infusion of graded levels of norepinephrine at rates of 1 to 3, 3 to 5, 5 to 8 and 8 to 10 <i>μ</i>g/min. Twelve patients subsequently died of pump failure during hospitalization. Control levels of stroke work produced excellent separation between survivors and nonsurvivors. The magnitude of maximal stroke work response during norepinephrine infusion in the two groups was also significantly different, but did not further separate the groups. However, the maximal percent change in stroke work in the two groups was similar, thus suggesting that, even in the presence of large infarcts, the remaining viable myocardium remains responsive to inotropic agents. Qualitatively the response of survivors and nonsurvivors was similar at low dose rates, but at a rate of 8 to 10 <i>μ</i>g/min, survivors exhibited predominantly an increase in stroke volume with little change in peripheral vascular resistance, whereas nonsurvivors showed predominantly an increase in peripheral vascular resistance with little change in stroke volume. We conclude that the initial level of ventricular function determines both the nature and magnitude of response to inotropic agents in acute myocardial infarction. Clinically, the usefulness of norepinephrine in this disease may be limited, since patients most likely to receive the drug would be expected to respond with a small increase in flow and a significant increase in afterload.

Optimal changes in stroke work during left ventricular bypass.

Optimal changes in stroke work during left ventricular bypass.

Hemodynamic and Metabolic Changes During Myocardial Ischemia

Alterations in ventricular performance during myocardial ischemia were assessed by relating changes in left ventricular enddiastolic pressures to simultaneous changes in stroke work. Myocardial ischemia, whether induced by exercise or by atrial pacing, was associated with depressed left ventricular function. When angina was prevented by the prior administration of nitroglycerin, ventricular function was normal. Data are presented to indicate the importance of left ventricular volume on the development of angina and to support the concept that a major action of nitroglycerin may be in reducing myocardial oxygen requirements by reducing left ventricular volume. Metabolic studies during pacing-induced angina show a close temporal relationship between the onset of angina, ventricular dysfunction, anaerobic metabolism, and electrocardiographic abnormalities. The prevention of angina by nitroglycerin therapy does not regularly improve the metabolic abnormalities.

EFFECT OF VARYING CORONARY PERFUSION ON VENTRICULAR FUNCTION IN ISOLATED DOG HEARTS.

The effects of coronary perfusion on ventricular function have been studied in isolated ventricle preparations working under different conditions. Coronary flow, oxygen consumption, ventricular stroke work, rate of ventricular pressure change during isovolumetric contraction (dPC), and diastolic ventricular pressure (DVPm) and pressure/inflow ratio were determined. Maintenance of coronary flow and oxygen consumption in 5 experiments did not prevent irreversible changes in DVPm, stroke work, and dPC when the right ventricle was acutely overloaded. These ventricles did not accumulate water. Decreasing coronary perfusion pressure at constant arterial oxygen content in 11 experiments led to inconsistent changes in DVPm, stroke work and dPC. Decreasing arterial oxygen content at constant coronary perfusion pressure in 10 experiments led to increased DVPm but inconsistent changes in stroke work and dPC. There was an inverse relationship between DVPm and oxygen consumption in the variable perfusion experiments, but not in the overloading experiments. Ventricular function did not change significantly with time in 6 experiments in which the conditions of workload and coronary perfusion were kept constant. It was concluded that irreversible changes in performance of acutely overloaded ventricles could be independent of coronary flow, myocardial water content, or duration of experiment.

THE STUDY OF LEFT VENTRICULAR FUNCTION IN MAN BY INCREASING RESISTANCE TO VENTRICULAR EJECTION WITH ANGIOTENSIN.

The performance of the left ventricle was studied in 18 patients by determining the effects of increasing the resistance to left ventricular ejection with graded infusions of angiotensin. By this means, left ventricular function curves, i.e., the relationship between ventricular end-diastolic pressure and stroke work, were constructed. In patients without left ventricular disease the ventricular function curves exhibited steep ascending limbs, large increases in stroke work occurring with small elevations of left ventricular end-diastolic pressure; in contrast, in patients with cardiac disease, the ventricular function curves were either flat, i.e., small changes in stroke work occurred with large elevations in left ventricular end-diastolic pressure, or the function curves exhibited descending limbs. Prior to the infusion of angiotensin many patients with and without depression of their left ventricular function curves had comparable values of left ventricular end-diastolic pressure and stroke work. Thus, the angiotensin test may prove useful for detecting impairment of myocardial function and for expressing the severity of the impairment in a quantitative form.

Action of digitalis on the nonfailing heart of the dog.

Ouabain induces a moderate increase in the contractility of the nonfailing heart of the dog with a complete circulatory system in doses which do not produce electrocardiographic signs of digitalis intoxication. The increased contractility was demonstrated both by the increase in ventricular contractile force and by the higher ventricular function curves obtained after administration of ouabain. The drug also increased systemic peripheral resistance and blood pressure, decreased systemic output, heart rate, left and right atrial pressures, and produced only small, variable changes in left ventricular stroke work. The reduction in systemic output and left atrial pressure and the absence of substantial changes in stroke work after ouabain appeared to be the result of a decrease in venous return to the heart. Evidence for this interpretation was obtained from experiments in which left atrial pressure was kept constant during the actions of ouabain by infusing 100–300 cc of whole blood. Under these conditions, ouabain brought about moderate increases in systemic output and left ventricular stroke work as well as in contractile force even though the changes in heart rate and blood pressure were comparable to those obtained in experiments in which left atrial pressure was uncontrolled. The data presented indicate that ouabain has two primary hemodynamic effects in the normal animal, namely, a direct cardiac stimulant action and a peripheral action resulting in a decreased venous return. The relationship of these findings to the mechanism of action of digitalis in congestive heart failure is discussed.

Direct measurement of changes in cardiac contractile force; relationship of such measurements to stroke work, isometric pressure gradient and other parameters of cardiac function.

Direct measurements of changes in the force of ventricular contraction with the strain gauge arch represent a sample of changes in the force of contraction of the entire ventricular muscle under conditions of an intact circulation. The responses of any given area of the ventricular muscle to repeated injections of the same dose of a cardiac stimulant drug are consistently similar. Further, there is a linear relationship between changes in the force of contraction as measured with the strain gauge arch and changes in the duration of the isometric pressure gradient. A direct relationship also exists between changes in contractile force and changes in stroke work. The relative advantages and limitations of the strain gauge arch and of the heart lever system, equipped with a strain gauge coil, are discussed in detail. Evidence is presented to show that the strain gauge arch is most useful in experiments in which substantial changes in the size of the heart do not occur. The heart lever system should be employed in experiments in which the size of the heart does undergo substantial change since adjustment may be made for changes in the initial diastolic fiber length. The time relations existing between direct recordings of contractile force made with the strain gauge arch and recordings of intravascular pressures have been demonstrated. A substantial portion of the contractile force is developed during the isometric phase of systole. There is a direct relationship between the amount of left ventricular contractile force developed during the isometric phase of contraction and the aortic diastolic pressure. A similar direct relationship exists between the total amount of contractile force measured by an arch on the left ventricle and the aortic systolic pressure. Mechanical stretching of the segment of muscle between the two points of attachment of the strain gauge arch produced length-tension curves which showed that a marked increase in contractile force occurs with increases in length of up to 40–60%. Stretching beyond these limits results in a progressive decrease in contractile force. The depth to which the sutures used in the attachment of the arch to the heart penetrated the myocardium has a moderate, but limited, quantitative influence upon the magnitude of contractile force measured. An arch attached with sutures penetrating deeply into the muscle measures more contractile force than an arch attached to the heart by superficially placed sutures.