Isolated Pericardial Hemodynamic Effects And Transplantation

Previous experiments have suggested that, in a normal intact heart at normal levels of right ventricular diastolic filling, the pericardium does not exert constraining effects on ventricular function (3,8). However, with increasing levels of right ventricular preload pressure, pericardial constraint increases, significantly influencing right ventricular function (17). By restricting atrial filling, the pericardium causes reductions in atrial systolic contributions to ventricular filling (18), mediated by atrioventricular interaction in addition to the direct ventricular interaction (8). In the left ventricle, at normal or only moderately elevated pressures, the pericardium has been reported to have a significant constraining effect on diastolic filling (19), often occurring without detectable changes in pericardial pressure (20,21). This suggests that, when normal cardiac limitations may be near maximum duress or capacity, such as during and following transplantation, the role of the pericardium may become more evident or prominent.

4.1. Four-Chamber Working In Vitro Model

With cardiac output physiologically dependent on diastolic pressure, in vitro, diastolic pressure and cardiac output can be controlled more without systemic influences. The sensitivity of the left ventricle to pericardial pressure is more evident given the differences in left ventricular performance with no significant difference in right ventricular performance associated with the effects of the pericardium. However, given the pericardial and chamber interactions, no attempt to separate or isolate the primary vs secondary pericardium effects on each chamber can be independently done.

In a study by our laboratory, we modeled pericardial effects during transplantation using swine hearts because of their anatomical and histological similarities to those of humans. The role of the pericardium hemodynamic function was investigated during and following simulated human orthotopic transplantation by use of an in vitro apparatus. This apparatus, capable of sustaining physiological cardiac function, was used to separate the pericardial influences from systemic effects and to simulate transplantation.

As detailed and documented in a previous study, the hemo-dynamic effects of explantation into the apparatus resulted in stability of ejecting parameters while working all four chambers (22). This is consistent with previous reports in which considerations of metabolic and contractile differences were observed between nonejecting and ejecting models; further, the role of the pericardium was noted with consideration to recovery of both left and right ventricular performance following an ischemic period (23,24).

Modified Krebs Henseleit buffer was used as perfusate with various additions to aid in maintenance of cardiac performance: ethylenediaminetetraacetic acid (EDTA) (0.32 mmol/L) to che-

Fig. 2. Experimental protocols for groups 1 and 2. In group 1, a pericardiotomy was performed previous to explantation into the apparatus. In group 2, explantation preceded pericardiotomy. During all phases, the heart was allowed to stabilize until hemodynamic parameters were measured. DC, data collection.

Fig. 2. Experimental protocols for groups 1 and 2. In group 1, a pericardiotomy was performed previous to explantation into the apparatus. In group 2, explantation preceded pericardiotomy. During all phases, the heart was allowed to stabilize until hemodynamic parameters were measured. DC, data collection.

late toxic metal ions and free calcium concentration titration; insulin (10 U/L) to aid in glucose utilization; sodium pyruvate (2.27 mmol/L) as an additional energy substrate; and mannitol (16.0 mmol/L) to increase osmolarity and reduce cardiac edema. The in vitro approach was employed because, in vivo, ventricular output is coupled to the pulmonary system and flows through the coronary vessels, limiting chamber ejection rates (i.e., right ventricle output cannot be steadily greater than left atrial output). Decoupling these flows in vitro allowed intrinsic output of the left and right side to operate independently with controlled atrial preload.

In one group of animals (n = 12), cardiac hemodynamic parameters were measured in situ following pericardiotomy and explantation into an in vitro apparatus. In a second group (n = 12), cardiac hemodynamic parameters were measured in situ following explantation in vitro and pericardiotomy (Fig. 2; see also MPEG 1 on the Companion CD.). Mean postmortem heart weights were statistically similar at 327 ± 3 g (group 1) and 346 ± 2 g (group 2). (See JPEG 1 on the Companion CD.)

Comparison of baseline cardiac parameters following medial sternotomy revealed no statistical difference between the two groups (p > 0.05 for both right and left ±dP/dt). Performance was dependent on the order of pericardiotomy and explantation. Differences existed between the two groups with final in vitro left ventricular +dP/dt (p < 0.001); no difference was observed in final in vitro right ventricular +dP/dt (p > 0.05). With in situ pericardiotomy, left and right ventricular +dP/dt changes of 5.1 ± 16.5% and 27.7 ± 31.4%, respectively, were observed vs 21.1 ± 11.8% and 21.6 ± 28.9%, respectively, with in vitro pericardiotomy. Concordantly, changes of -2.7 ± 18.6% and 5.1 ± 20.1%, respectively, were observed in left ventricular +dP/dt associated with explantation following in situ pericar-diotomy, compared to -2.0 ± 7.5% and 5.5 ± 24.5%, respectively, following in vitro pericardiotomy.

Several significant differences were associated with final in vitro cardiac performance with and without the pericardium in values of left ventricular +dP/dt (1126.1 ± 110.1 vs 925.3 ±

Fig. 3. Results detailing the effects of transplantation in vitro with and without the pericardium (n = 12 per set). In situ baseline control, pericardiotomy, and explantation in vitro maximum ±dP/dt performance characteristics as indicators of ventricular contractility and relaxation are shown.

117.7, respectively; p < 0.05) and -dP/dt (1116.4 ± 159.9 vs 859.2 ± 174.5, respectively) and in right ventricular -dP/dt (192.6 ± 33.6 vs 221 ± 39.8, respectively). No differences in right ventricular +dP/dt were observed between removing the pericardium in situ vs in vitro.

These findings indicated that an intact pericardium has a depressive influence on normal left ventricular performance and may help preserve left ventricular systolic function as measured by left ventricular +dP/dt following transplantation, but that these relative effects were not equivalent for both ventricles. The nonsymmetrical results between the left and right ventricles under constant filling preload and afterload resistance supported the notion that chamber reaction of one ventricle oppositely affects the other chamber because of interactions across the free wall. Yet, previous studies including both human and animal models have assumed similar in situ and in vitro function independent of the pericardium. Based on these findings, care should be taken when interpreting hemodynamic results with respect to the absence or presence of the pericardium, especially when the ratio of forces because of pericardial constraint affecting diastolic filling is unknown.

In group 1 (in situ pericardiotomy and explantation in vitro), a medial sternotomy was performed, and the rib cage was retracted, preserving the integrity of the pericardial sac, which was freed from the surrounding interthoracic tissues. In situ data were recorded to measure myocardial performance with rib cage pressure relieved. Following pericardiotomy, including all connective tissue and fat, hemodynamic measurements were then repeated as outlined above.

The hemodynamic effects were normalized with respect to the previous stage by calculating percentage of change associated with each procedure. In addition, the percentage change between initial in situ values and final in vitro values were determined. Group 1 in situ baseline data, the effects of in situ pericardiotomy, and the effects of explantation in vitro in the absence of the pericardium are shown in Fig. 3 and Table 1.

Table 1

Mean ± SD (n = 12)

Baseline (in situ)

Postpericardiotomy (in situ)

Postexplantation (in vitro)

Group 1

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