Operative procedure and volumetry in experimental biomechanical hearts.

BACKGROUND: To date, skeletal muscle ventricles (SMVs) have been integrated into the circulation by a second operation following construction, vascular delay and several weeks of electrical conditioning. Recently, intra-thoracic SMVs around a mock system contracted against a pressure of 70 mmHg for several months immediately after construction in the presence of clenbuterol. This indicates that the two-step procedure may be exchanged for a clinically favorable one-step operation. The stroke volume is tested intra-operatively. METHODS: In twelve Boer goats, the latissimus dorsi muscle was folded in a double layer around a polyurethane chamber, which was integrated into descending thoracic aorta. This muscular flow-through chamber containing a stabilizing inner layer denoted "Biomechanical Heart" (BMH) showed immediate activity against systemic pressure. The conductance catheter method was applied for analysis of intra-operative stroke volume. RESULTS: The one-step operative procedure employed was practicable in all 12 goats. Operative complications were eliminated without difficulty. Intraoperative application of the conductance catheter resulted in BMH with a stroke volume of 55 +/- 14 ml. In the best BMH on postoperative day 132, a continuous pumping capacity of 1.4 l/min was measured. This BMH functioned up to day 414 postoperatively, and failed due to a rupture of the pumping chamber. CONCLUSION: This operative procedure and dynamic volumetry of experimental Biomechanical Hearts might be relevant for clinical use.

Biomechanical hearts: muscular blood pumps, performed in a 1-step operation, and trained under support of clenbuterol.

BACKGROUND: As shown previously in goats, clenbuterol increased the power of electrically conditioned skeletal muscle ventricles (SMVs) of clinically relevant size (150 mL), which were constructed around a mock system. They pumped against a pressure of 60 to 70 mm Hg immediately during surgery and up to several months after, finally at >1 L/min. SMVs without clenbuterol administration failed. Thus, we expected that clenbuterol-supported SMVs might become integrated into the circulation by a 1-step operation instead of the 2-step procedure required up to now. METHODS AND RESULTS: In adult Boer goats (n=5), latissimus dorsi muscle was wrapped around a polyurethane chamber of 150 mL that was connected to the descending aorta. This muscular flow-through pumping chamber containing a stabilizing inner layer (called a biomechanical heart [BMH]) was formed and immediately made to work against a systemic load with the support of clenbuterol (5x150 microg/wk). During surgery, the mean stroke volume of BMHs was 53.8+/-22.4 mL. One month after surgery, in peripheral arterial pressure, the mean diastolic (P(MD)) and minimal diastolic (P(min)) pressures of BMH-supported heart cycles differed significantly from unsupported ones (P(MD)=+2.9+/-1.1 mm Hg [P<0.04], P(min)=-2.4+/-0.9 mm Hg [P<0.04]). After BMH-supported heart contractions, the subsequent maximal rate of pressure generation, dP/dt(max), increased by 20.5+/-8.1% (P<0.02). One BMH, catheterized 132 days after surgery, shifted a volume of 34.8 mL per beat and 1.4 L/min with a latissimus dorsi muscle of 330 g. Depending on duration of training, the percentage of myosin heavy chain type 1 ranged between 31% and 100%. CONCLUSIONS: Under support of clenbuterol, BMHs of a clinically relevant size can be trained effectively in the systemic circulation after a 1-step operation and offer the prospect of a sufficient volume shift and probably unloading of the left ventricle.

Clenbuterol-supported dynamic training of skeletal muscle ventricles against systemic load: a key for powerful circulatory assist?

BACKGROUND: The profound loss of power that occurs in skeletal muscle after electrical conditioning has been the major limiting factor in its clinical application. This study investigates a 3-fold approach for chronic conditioning of skeletal muscle ventricles (SMVs) combining electrical transformation, dynamic training against systemic load, and pharmacological support with clenbuterol. METHODS AND RESULTS: In 10 adult male goats, SMVs were constructed from latissimus dorsi muscle wrapped around an intrathoracic training device with windkessel characteristics. SMVs were stimulated electrically and trained dynamically by shifting volume against systemic load. Group 1 goats were controls (n=5), and group 2 goats (n=5) were supported with clenbuterol (150 microg 3 times a week). SMV dynamics were recorded weekly over 5 to 8 months: peak pressure (P(max)), stroke volume (SV), volume displacement per minute (VD), stroke work per day (SW/d), and maximum rates of pressure generation, +dP/dt(max), and decay, -dP/dt(max). In group 1, after 149.5+/-2.7 days (n=4), data were P(max)=70.8+/-4.7 mm Hg, SV=3.2+/-1.2 mL, VD=62.3+/-21.1 mL/min, SW/d=0.8+/-0.4 kJ, +dP/dt(max)=64+/-13 mm Hg/s, and -dP/dt(max)=156+/-32 mm Hg/s. These parameters were significantly improved (P<0.007) in the clenbuterol-treated group 2 after 151+/-2.7 days: P(max)=176.2+/-43.8 mm Hg, SV=23.3+/-6.1 mL, VD=568.2+/-186.1 mL/min, SW/d=9.1+/-2.2 kJ, +dP/dt(max)=1134+/-267 mm Hg/s, and -dP/dt(max)=1028+/-92 mm Hg/s. In 2 SMVs of group 2, VD increased to 1090 and 1235 mL/min after 202 and 246 days of training, respectively. At termination, myosin heavy chains were totally transformed into myosin heavy chain-1 in all SMVs. CONCLUSIONS: This clenbuterol-supported dynamic training provides powerful SMVs that may have important clinical implications for the treatment of end-stage heart failure by muscular blood pumps.

An in-vitro evaluation of aortic arch vessel perfusion characteristics comparing single versus multiple stream aortic cannulae.

OBJECTIVE: During extracorporeal circulation design and orientation of aortic cannulae tips mainly determine flow pattern in the aortic arch and arch vessels which is the objective of this in vitro study, comparing single versus multiple stream cannulae. METHODS: In an aortic arch glass model, jet streams of 21-24 French aortic cannulae which were inserted in the ascending aorta were directed alternatively at the different arch vessels. Flows and pressures in the arch vessels were measured at pump flows of 3-6 l/min. RESULTS: With optimal orientation of the jet stream in the aortic arch, no preferential flow in the arch vessels was seen. In the single jet stream aortic cannulae group a significant parallel increase in flow and pressure in the jet streamed arch vessels compared to the non-jet streamed arch vessels occurred (P < 0.05). With the jet stream directed on vessel 2 (left carotid vessel) there was a significant pressure and flow difference comparing the two non-jet streamed vessels with each other (P < 0.03). In the single stream 24 French cannulae the highest vessel pressure of 168 mmHg and an increase in flow of 186 ml/min was measured in the jet streamed left carotid artery at 6 l/min pump flow. The multiple stream cannulae provoked the highest vessel pressure of 106 mmHg in the corresponding jet streamed vessel and an increase in flow of 20 ml/min. CONCLUSION: Tip design of aortic cannulae and the orientation of its jet stream are potential sources of remarkable imbalance of arch vessel perfusion especially with single jet stream cannulae. These effects are more pronounced with single jet stream cannulae. These results may have important clinical implications regarding perfusion of arch vessels during extracorporeal circulation.

Stroke volume validation and energy evaluation for the dynamic training of skeletal muscle ventricles.

Skeletal muscle ventricles used for cardiac assistance were trained dynamically by shifting volume within an elastic training device. To optimize this dynamic training that is by variation of stimulation patterns and application of drugs, methods for stroke volume and energy evaluation were required. A volume shift induced by a muscle contraction resulted in a pressure rise in the training device. Stroke volume was calculated by relating the pressure difference of a muscle contraction to the device's compliance. For validation of the calculated stroke volume, a mock system was built to simulate muscle contractions under various conditions. The stroke volume measured independently and calculated by means of the pressure rise inside the training device, showed an approximately one-to-one relation (R=0.996). Calculation of delivered energy from skeletal muscle ventricles thereby became possible. This method offers a simple, reliable and practical procedure to quantify the dynamic training of skeletal muscle ventricles for use in cardiac assistance.

New method for monitoring the functional state of a dynamic cardiomyoplasty.

OBJECTIVE: To assess the impact of a dynamic cardiomyoplasty on failing hearts, it is essential to estimate the contraction force of the skeletal muscle and how its contraction is synchronized with the heart cycle. METHODS: In a 6-month study a small fluid-filled, balloon-mounted catheter was placed between the myocardium and the muscular wrap in five adult female Boor goats and two female domestic pigs. The catheter was connected to a subcutaneous measuring chamber whereby pressure monitoring could be accomplished. Distinct pressure signals as a result of function of the dynamic cardiomyoplasty and the heart were detected initially in all animals. RESULTS: Maximal relative pressure from the dynamic cardiomyoplasty was calculated as 336.2% +/- 69.4% on day 24 +/- 6.1 (n = 7) and end-stage pressure as 59.8% +/- 9.7% on day 174.6 +/- 13.1 (n = 4). A functional loss of pressure signals from the dynamic cardiomyoplasty was correlated to severe histologic muscle damage (n = 3). Pressure signals transferred from the contracting myocardium to the catheter showed defined segments of contraction, ejection, and filling periods, allowing a mechanical synchronization of the dynamic cardiomyoplasty to the heart cycle. CONCLUSIONS: This monitoring catheter enabled the assessment of the functional state of the dynamic cardiomyoplasty and allowed a synchronization to the heart cycle. It will promote understanding and might help to avoid muscle damage in dynamic cardiomyoplasty for an improved outcome of the surgical treatment of end-stage heart failure.

Dynamic training of skeletal muscle ventricles. A method to increase muscular power for cardiac assistance.

BACKGROUND: Skeletal muscle can be used for cardiac assistance after electrical stimulation over a period of several weeks. This will adapt it to do chronic work with no resulting fatigue. The result of this procedure, however, is a reduction of 80% in muscle power, > 60% in muscle mass, and approximately 85% in contractile speed. To minimize these disadvantages, the following study was done to develop and test a method to dynamically train skeletal muscle ventricles (SMVs). METHODS AND RESULTS: Barrel-shaped SMVs were tested in 15 Jersey calves. They were made from the latissimus dorsi muscle, which was wrapped around an elastic silicone training device. Six SMVs were used extrathoracically in a single layer and nine intrathoracically in a double layer. With dynamic training preserving contractile speed, the output increased to approximately 5 L/min, the systolic pressure increased to > 200 mm Hg, and power developed to approximately 10 W after 3 months of dynamic training. The contractile speed of dynamically trained SMVs was between 250 and 700 mm/s. The diameter of the latissimus dorsi muscle increased to three times that of the corresponding contralateral muscle. CONCLUSIONS: The combination of electrical conditioning with dynamic training of the SMVs resulted in a strong muscle pump that did not develop fatigue. Dynamic training for skeletal muscle represents a new and promising method for providing powerful autologous cardiac assist.