Load dependence of cardiac output in biventricular pacing: right ventricular volume overload in pigs

BACKGROUND: Previous work from our laboratory has demonstrated that optimization of biventricular pacing is load dependent. During acute pulmonary stenosis and right ventricular pressure overload in swine, cardiac output was maximized by pacing the right ventricle 40 ms before the left ventricle. To extend those studies, this experiment examined biventricular pacing optimization during right ventricular volume overload. METHODS: After median sternotomy in 6 anesthetized domestic pigs, complete heart block was induced by ethanol ablation. A conduit was grafted from the right ventricle to the right atrium to simulate tricuspid insufficiency. During epicardial, atrial tracking DDD biventricular pacing, atrioventricular delay was varied between 60 and 180 ms in 30-ms increments. Right ventricular-left ventricular delay was varied at each atrioventricular delay from +80 ms (right ventricle first) to -80 ms (left ventricle first) in 20-ms increments. Aortic flow, right ventricular pressure, and electrocardiogram were measured at each pacemaker setting with the graft clamped and unclamped. RESULTS: Atrioventricular and right ventricular-left ventricular delays had no significant effect on cardiac output with the graft clamped. With the graft unclamped, however, there was a statistically significant (P =.003 by mixed modeling repeated measures analysis of variance) trend toward higher cardiac output with left ventricle-first pacing. CONCLUSION: Left ventricle-first biventricular pacing in swine significantly increased cardiac output during acute tricuspid insufficiency but not during the control state. Trials are warranted to develop clinical biventricular pacing for treatment of perioperative right ventricular dysfunction.     

Impact of biventricular and left ventricular pacing on hemodynamics and left ventricular dyssynchrony compared with right ventricular pacing in the early postoperative period following cardiac surgery

Objectives

The aims of this study were to test the hypotheses that in the postoperative period following corrective surgery for congenital heart defects: (i) atrio-right ventricular (RA-RV) pacing decreases cardiac output (CO) compared with right atrial (RA) pacing, (ii) atrio-biventricular (RA-BiV) and left ventricular (RA-LV) pacing improves CO compared with RA-RV pacing.

Study design

Prospective observational study.

Patients

Children 0-2 years of age referred for surgery of congenital heart defects were studied during intrinsic rhythm and atrial, atrio-right ventricular, atrio-left ventricular and atrio-biventricular pacing. CO, extrapolated from mean systolic aortic velocity (MSAV), and left ventricular dyssynchrony were assessed using transthoracic echocardiography.

Results

RA-RV pacing induced a significant decrease in CO (MSAV 0.52 ± 0.19 m/s to 0.46 ± 0.16 m/s, p = 0.01) and a significant increase in LV dyssynchrony (8.7 ± 7.9 ms to 33 ± 21 ms, p = 0.001). RA-BiV pacing induced a significant increase in CO (MSAV 0.46 ± 0.16 m/s to 0.52 ± 0.18 m/s, p = 0.01) and a significant decrease in LV dyssynchrony (33 ± 21 ms to 7 ± 4 ms, p = 0.0003) compared with RA-RV pacing. RA-LV pacing induced a significant decrease in LV dyssynchrony (33 ± 21 ms to 9 ± 7 ms, p = 0.0007) without a significant improvement of CO compared with RA-RV pacing.

Conclusions

RA-BiV pacing improves CO compared with RA-RV pacing in the early postoperative period following pediatric cardiac surgery. This improvement is related to a reduction in left ventricular dyssynchrony.     

Impact of pacing modality and biventricular pacing on cardiac output and coronary conduit flow in the post-cardiotomy patient

We have previously demonstrated the role of univentricular pacing modalities in influencing coronary conduit flow in the immediate post-operative period in the cardiac surgery patient. We wanted to determine the mechanism of this improved coronary conduit and, in addition, to explore the possible benefits with biventricular pacing. Sixteen patients undergoing first time elective coronary artery bypass grafting who required pacing following surgery were recruited. Comparison of cardiac output and coronary conduit flow was performed between VVI and DDD pacing with a single right ventricular lead and biventricular pacing lead placement. Cardiac output was measured using arterial pulse waveform analysis while conduit flow was measured using ultrasonic transit time methodology. Cardiac output was greatest with DDD pacing using right ventricular lead placement only [DDD-univentricular 5.42 l (0.7), DDD-biventricular 5.33 l (0.8), VVI-univentricular 4.71 l (0.8), VVI-biventricular 4.68 l (0.6)]. DDD-univentricular pacing was significantly better than VVI-univentricular (P=0.023) and VVI-biventricular pacing (P=0.001) but there was no significant advantage to DDD-biventricular pacing (P=0.45). In relation to coronary conduit flow, DDD pacing again had the highest flow [DDD-univentricular 55 ml/min (24), DDD-biventricular 52 ml/min (25), VVI-univentricular 47 ml/min (23), VVI-biventricular 50 ml/min (26)]. DDD-univentricular pacing was significantly better than VVI-univentricular (P=0.006) pacing but not significantly different to VVI-biventricular pacing (P=0.109) or DDD-biventricular pacing (P=0.171). Pacing with a DDD modality offers the optimal coronary conduit flow by maximising cardiac output. Biventricular lead placement offered no significant benefit to coronary conduit flow or cardiac output.     

Temporary and permanent biventricular pacing via left ventricular epicardial leads implanted during primary cardiac surgery

OBJECTIVES: Biventricular pacing (BVP) is a new strategy for treating patients with severe congestive heart failure (CHF) and intraventricular conduction delay, but its full potential and technicalities of BVP require further evaluation. We evaluated BVP benefits in 4 patients in whom we implanted a left ventricular lead during primary cardiac surgery. METHODS: Four CHF patients treated surgically between October 2000 and August 2001 underwent, at primary surgery, the implantation of leads in the right atrium, right ventricle, and left ventricle (LV) for postsurgical BVP. All patients had severe LV dysfunction and dilatation with intraventricular conduction delay. Surgeries involved CABG alone (n = 1), CABG + Dor's operation (n = 2), and tricuspid valve replacement + Maze procedure (n = 1). BVP was begun immediately after surgery in all 4 patients. Hemodynamic variables with BVP were compared to those without BVP for each patient, and the utility and technical aspects of implantation were evaluated. RESULTS: BVP increased mean systemic blood pressure by 11% and mean LV stroke work index by 19% in the acute postsurgery period, and reduced mitral regurgitation. Two of the patients were implanted with a generator for permanent BVP, one at 1 month and the other at 6 months after surgery. The threshold of the LV epicardial lead of these 2 patients was below 2 V during follow-up, and BVP was successful. CONCLUSIONS: Temporary BVP during the short-term after cardiac surgery improved cardiac function and decreased mitral regurgitation in all 4 of our patients. Epicardial lead implantation may thus be a useful option during surgical treatment of patients with CHF and intraventricular conduction delay if long-term permanent BVP is indicated.     

Maintained cardiac output during positive end-expiratory pressure ventilation in open-chest pigs

Background: Does ventilation with positive end-expiratory pressure (PEEP) act to reduce cardiac output (CO) not only by impeding venous return but also by inducing myocardial depression? The present study was aimed to demonstrate the possible existence of this latter mechanism. Methods: Eight pigs of Swedish native breed weighing 20–25 kg and 10–12 weeks old were anaesthetized, tracheotomized and connected to a volume-controlled ventilator. To prevent intra-thoracic pressure from interfering with venous return, the heart and juxtacardiac vessels were exposed to atmospheric pressure by opening and retracting the chest and pericardium. Heart rate (HR), CO, stroke volume (SV), mean arterial (MAP), mean right (MRAP) and left (MLAP) atrial pressures were recorded before and after retransfusion of 500 ml of autologous blood. This procedure was carried out twice in each animal - during ventilation with zero and with 15 cm H₂O of PEEP. Results: Comparison of the two ventilation modes before volume load revealed negligible differences in HR, CO, SV, MAP, MRAP and MLAP. Moreover, the changes evoked by volume load were practically identical. Conclusions: Addition of PEEP to regular positive pressure ventilation does not induce any haemodynamically detectable myocardial depression in the piglet.     

Concurrent left and right ventricular hypertrophy in dog models of right ventricular overload

In two pressure and volume overload models of canine right ventricular hypertrophy, we have demonstrated significant hypertrophy of both the left and the right ventricles. The extent of hypertrophy was correlated positively to the extent of the increase in plasma epinephrine in both volume and pressure overload models. Attenuation or ablation of plasma epinephrine through the administration of propranolol, a beta-adrenergic blocker, or by denervation of the adrenal medulla prevented the hypertrophy process. No hemodynamic parameter was altered consistently in a parallel manner to hypertrophy. This is the first report of concurrent right and left ventricular hypertrophy in response to pressure or volume overload of the right ventricle. These studies further implicate epinephrine as a major trophic hormone of the heart.     

Rapid ventricular pacing: a novel technique to decrease cardiac output for giant basilar aneurysm surgery

A case of a 49 year old man with a giant basilar artery aneurysm requiring rapid ventricular pacing is presented. Rapid ventricular pacing decreased aneurysm size and increased operative exposure, which aided surgical decision making. It also provided decreased wall tension in the aneurysm.     

Robotically assisted left ventricular epicardial lead implantation for biventricular pacing: the posterior approach

Patients with congestive heart failure and altered interventricular conduction enjoy improvements in quality of life and ventricular function after successful resynchronization therapy with biventricular pacing. Technical limitations owing to individual coronary sinus and coronary venous anatomy result in a 10% to 15% failure rate of left ventricular (LV) lead placement through percutaneous approaches. To provide a minimally invasive option for these patients with LV lead failures, we developed a technique of endoscopic, epicardial LV lead implantation with the use of the da Vinci robotic system. The surgical approach targets the posterolateral wall through a novel posterior approach.     

Stem cells improve right ventricular functional recovery after acute pressure overload and ischemia reperfusion injury

BACKGROUND: In many clinical scenarios, a relatively untrained right ventricle may be subjected to acute elevations in pulmonary artery and right ventricular pressures. The right and left heart are distinctly different in this regard and there is currently no in vivo model to study right ventricular ischemia in the setting of acute pressure overload. In acute injury, cardiomyocytes produce tumor necrosis factor, which mediates a proinflammatory pathway, eventually leading to myocardial dysfunction. Stem cells have been shown to reduce the production of proinflammatory mediators by the ischemic myocardium and protect the myocardium. Pretreatment with stem cells has been shown to protect the left ventricle. The effect of acute pressure overload to the untrained right ventricle is still not well understood. Furthermore, it is unclear whether pretreatment with stem cells would protect the right ventricle when it is subjected to acute pressure overload and concomitant ischemia reperfusion injury. The purpose of this study was (1) to create a simple model of acute pressure overload for the study of concomitant right ventricular ischemia and reperfusion, and (2) to evaluate the effect of pretreatment with stem cells prior to ischemia reperfusion injury. MATERIALS AND METHODS: Isolated rat hearts were perfused with the modified Langendorff technique with the latex balloon in the right ventricle instead of the left, with a pressure-transduced balloon being used to create an acute elevation in right ventricular pressure before ischemia. In the first of a two-series experiment, there were two experimental groups (N = 8 per group): one with right ventricular balloon end-diastolic pressure (EDP) of 5 mmHg (physiological), and the other with an EDP of 40 mmHg (pathologic). In the second series, the hearts with the higher balloon pressure (EDP 40 mmHg) were divided into two experimental groups (N = 5 per group). The control group was not pretreated. One group was pretreated with human mesenchymal stem cells 5 min immediately prior to ischemia reperfusion injury. Right ventricular developed pressure (RVDP), contractility (+dP/dt), and compliance (-dP/dt) were continuously assessed. Additionally, mesenchymal stem cells (MSCs) in culture were stressed by hypoxia and activation was determined by measuring vascular endothelial growth factor-A (VEGF) and hepatocyte growth factor (HGF) production by enzyme-linked immunosorbent assay. RESULTS: Recovery of RVDP, +dP/dt, and -dP/dt was significantly higher (P < 0.001) in the group with lower EDP compared to the group with the higher EDP [RVDP: 79.53 +/- 6.34 versus 54.28 +/- 10.76%; +dP/dt: 76.54 +/- 8.79 versus 38.75 +/- 19.74%; -dP/dt: 72.29 +/- 7.02 versus 30.54 +/- 12.44%]. In the higher EDP groups, pretreatment with human mesenchymal stem cells significantly improved myocardial function recovery (P < 0.01) when compared to controls [RVDP: 75.76 +/- 7.97 versus 59.10 +/- 11.18%; +dP/dt: 71.78 +/- 10.36 versus 54.93 +/- 12.64%; -dP/dt: 77.38 +/- 11.09 versus 59.30 +/- 15.20%]. Further, hypoxic MSCs demonstrated significantly greater VEGF and HGF release than controls. CONCLUSION: This compounded injury model allowed the study of right ventricular dysfunction in the setting of acute pressure overload and ischemia. Additionally, we have also demonstrated that pretreatment with stem cells of an acutely pressure overloaded right ventricle prior to ischemia reperfusion injury improves functional recovery. This is the first report of a modified Langendorff technique to study right ventricular function in the setting of acute pressure overload and ischemia and the effect of pretreatment with stem cells.