Ralph J Damiano

Robotically assisted microsurgery for endoscopic coronary artery bypass grafting

BACKGROUNDnAs minimally invasive approaches to cardiac surgery have expanded, a significant number of limitations have become apparent, particularly the lack of adequate precision with standard endoscopic instruments. We hypothesized that the use of robotics would eliminate some of these limitations.nnnMETHODSnTwenty-five coronary anastomoses on an isolated porcine heart, using an arterial conduit to the left anterior descending artery, were performed endoscopically with a microsurgical robotic system. Sophisticated robotic engineering was used to control modified endoscopic instruments under direct surgeon control. Computer tremor elimination and motion scaling allowed for precise maneuvering. An arteriotomy was placed in the left anterior descending artery, and an arterial conduit was positioned for anastomosis. The camera and port sites were placed 90 degrees from the long axis of the arteriotomy. A 7-0 Prolene (Ethicon, Somerville, NJ) suture was used to perform the anastomosis in a continuous fashion, begun at the 12 oclock position and continued counterclockwise. After completion of half of the anastomosis, the conduits were pulled down and the final sutures were placed. The sutures were tied intracorporeally and the procedure was completed.nnnRESULTSnThe 25 conduits were successfully completed and showed good probe patency. Average time for completion of the anastomosis was 31.7 +/- 2.0 minutes. Appropriate port placement and orientation, and stabilization of the conduits were critical. The lack of tremor and motion scaling allowed for the precise movements needed to complete an endoscopic microvascular anastomosis.nnnCONCLUSIONSnCoronary artery anastomoses are technically feasible with use of robotic instrumentation. This technology may enable the development of a truly endoscopic approach to bypass surgery.

Potassium-channel opener cardioplegia is superior to St. Thomas’ solution in the intact animal

BACKGROUNDnIn isolated hearts, the potassium-channel opener pinacidil is an effective cardioplegic agent. This study tested the hypothesis that pinacidil is superior to St. Thomas solution in the more clinically relevant intact animal.nnnMETHODSnSixteen pigs were placed on full cardiopulmonary bypass. Hearts underwent 2 hours of global ischemia (10 degrees to 15 degrees C). Either St. Thomas or 100 micromol/L pinacidil was administered every 20 minutes (10 mL/kg). Preischemic and postreperfusion slopes of the preload-recruitable stroke work relationship were determined. Changes in myocardial adenine nucleotide levels and cellular ultrastructure were analyzed.nnnRESULTSnPinacidil cardioplegia resulted in an insignificant change in the slope of the preload-recruitable stroke work relationship (40.6+/-2.1 mm Hg/mm before ischemia and 36.5+/-3.7 mm Hg/mm after ischemia; p = 0.466). In contrast, St. Thomas solution resulted in a significant decrease in the slope after reperfusion (34.3+/-5.5 mm Hg/mm and 13.5+/-2.3 mm Hg/mm; p = 0.003). Adenine nucleotide levels, myocardial tissue water, and ultrastructural changes were similar between groups.nnnCONCLUSIONSnPinacidil ameliorated myocardial stunning associated with traditional hyperkalemic cardioplegia without causing significant differences in cellular metabolism.

Computer-assisted endoscopic coronary artery bypass anastomoses: a chronic animal study.

BACKGROUNDnWith traditional instruments, endoscopic coronary artery bypass grafting (ECABG) has not been possible. This study was designed to determine the feasibility of using a robotically-assisted microsurgical system to perform ECABG in a chronic animal model.nnnMETHODSnNine calves were placed on cardiopulmonary bypass after harvesting the left internal mammary artery (LIMA). Subxiphoid endoscopic ports (2 instrument, 1 camera) were placed, and a robotic system was used to perform ECABG between the LIMA and left anterior descending coronary artery. LIMA graft flow (LIMAQ) was measured. Animals were sacrificed at 1 month, and hearts underwent angiographic and histologic analyses.nnnRESULTSnAcute graft patency was 89% (8/9). Two animals died suddenly within the first 48 hours. There was no significant difference in mean acute and chronic (n = 6) LIMAQ (40.9+/-4.7 and 38.5+/-5.0 ml/min, respectively). Survivors had an angiographic patency rate of 100% (6/6), confirmed by histology.nnnCONCLUSIONSnThis study shows that ECABG is feasible in a chronic animal model with excellent results.

2,3-Butanedione monoxime cardioplegia : Advantages over hyperkalemia in blood-perfused isolated hearts

BACKGROUNDn2,3-Butanedione monoxime (BDM) has been shown to possess cardioprotective properties related to the inhibition of cross-bridge force development, the reduction of myofilament Ca2+ sensitivity, and the attenuation of intracellular Ca2+ transients. This study tested the hypothesis that cardiac arrest achieved with BDM would be as effective as that achieved with St. Thomas solution (StT).nnnMETHODSnIsolated rabbit hearts, studied on a blood-perfused Langendorff column, underwent 1 hour of ischemia (37 degrees C) and 30 minutes of reperfusion. Cardioplegia was administered every 20 minutes in the form of (1) Krebs-Henseleit solution only (control), (2) 20 mmol/L of BDM, or (3) StT. Recovery of developed pressure, atrioventricular activation times, and tissue water content were measured.nnnRESULTSnRecovery of developed pressure for the control, BDM, and StT groups was 44%+/-3% (p<0.05 versus BDM and StT), 57%+/-5%, and 62%+/-4%, respectively. Atrioventricular activation times were significantly prolonged in the control group (42+/-15 ms, p = 0.042) and the StT group (26+/-9 ms, p = 0.034), but not in the BDM group (14+/-8 ms). Tissue water content after reperfusion was 80%+/-0.4%, 80%+/-0.2%, and 76%+/-1.0% (p<0.05 versus control) in the control, StT, and BDM groups, respectively.nnnCONCLUSIONSn2,3-Butanedione monoxime was as effective as StT in protecting the myocardium. Unlike StT, BDM ameliorated myocardial edema and atrioventricular conduction delay after reperfusion.

Donor heart preservation with the potassium channel opener pinacidil: comparison with University of Wisconsin and St. Thomas’ solution

BACKGROUNDnHyperpolarized arrest with the potassium channel opener pinacidil has been shown to provide effective myocardial protection during short-term global ischemia. This study tested the hypothesis that pinacidil may provide effective long-term protection for heart transplant preservation.nnnMETHODSnFour concentrations of pinacidil (50 microM, 100 microM, 0.5 mM, 1.0 mM) mixed in Krebs-Henseleit solution were compared with University of Wisconsin and St. Thomas Hospital solutions in a Krebs-Henseleit perfused rabbit Langendorff model (n = 6 for each group). Hearts underwent 4 hours of hypothermic (4 degrees C) storage. Over a wide range of volumes, left ventricular systolic function, diastolic compliance, and coronary flow were measured prior to and following storage. Time to mechanical and electrical arrest, and post-ischemic percent tissue water were also measured.nnnRESULTSnPinacidil 0.5 mM provided the best preservation of post-ischemic systolic function and coronary flow compared with the other pinacidil concentrations and was statistically equivalent to St. Thomas solution in terms of post-ischemic systolic, diastolic, and flow properties. However, hearts protected with University of Wisconsin solution had significantly better preservation of systolic function and coronary flow.nnnCONCLUSIONSnThis investigation demonstrated that pinacidil in Krebs-Henseleit solution possesses efficacy in long-term donor heart preservation. Pinacidil was equivalent to St. Thomas solution but inferior to University of Wisconsin solution. Hyperpolarized arrest with potassium channel openers may be a novel strategy to improve donor heart preservation.

Superior 12-hour heart preservation with pinacidil hyperpolarizing solution compared to University of Wisconsin solution☆

BACKGROUNDnnovel donor heart preservation solution was formulated to produce hyperpolarized arrest with the potassium channel opener, pinacidil. The superior cardioprotective efficacy of this solution has been demonstrated previously when compared to University of Wisconsin solution following 4 hours of hypothermic ischemia. This study tested the hypothesis that pinacidil solution may extend preservation time and provide superior cardioprotective efficacy following 12 hours of ischemia.nnnMETHODSnSixteen rabbit hearts were assigned to receive either pinacidil solution or University of Wisconsin solution in a crystalloid-perfused Langendorff model. Thirty minutes of initial perfusion preceded baseline data acquisition. Left ventricle pressure-volume curves were generated by inflating an intra-ventricular latex balloon. Following cardioplegic administration, hearts underwent 12 hours of hypothermic storage. After 60 minutes of reperfusion, post-ischemic data were acquired.nnnRESULTSnPinacidil solution demonstrated significantly better myocardial preservation compared to University of Wisconsin solution, with better recovery of developed pressure (53.0 +/- 11.1% vs 20.7 +/- 4.3%, p = 0.017, respectively), post-ischemic coronary flow (55.3 +/- 12.6% vs 23.9 +/- 4.3%, p = 0.034), maximum systolic dP/dT (46.4 +/- 8.3% vs 20.2 +/- 5.1%, p = 0.018) and minimum diastolic -dP/dT (65.3 +/- 10.8% vs 20.2 +/- 5.1%, p = 0.002). Diastolic compliance, expressed as baseline/post-ischemic diastolic slope ratios, was also better preserved by pinacidil solution (0.55 +/- 0.09) vs University of Wisconsin solution (0.40 +/- 0.03) (p = 0.135).nnnCONCLUSIONSnA novel pinacidil solution resulted in improved donor heart preservation during 12 hours of hypothermic ischemia compared to the gold standard, University of Wisconsin solution. Adopting alternative strategies of hyperpolarized arrest may allow extension of preservation time beyond the limits of traditional depolarizing solutions.

Potassium channel openers: are they effective as pretreatment or additives to cardioplegia?

BACKGROUNDnThis study was designed to test the hypothesis that the potassium channel opener pinacidil (Pin) as a pretreatment (PT) agent or additive to St. Thomas solution (StT) could enhance myocardial protection.nnnMETHODSnIn a parabiotic rabbit Langendorff model, 36 hearts underwent global normothermic ischemia (1 hour) followed by reperfusion (30 minutes). Cardioplegia (50 mL, every 20 minutes) consisted of: StT; PinPT/StT, where Pin PT preceded StT arrest; Pin alone; Pin in StT (Pin/StT); and Pin in low potassium StT. Systolic function after reperfusion (percent recovery of developed pressure) and compliance (diastolic slope from pressure-volume relationship) were measured.nnnRESULTSnThere was no significant difference between StT and PinPT/StT in percent recovery of developed pressure (51.54% +/- 3.5%, 42.17% +/- 4.0%, respectively) or compliance. Likewise, no significant differences occurred between Pin, StT, Pin/StT, and Pin in low potassium StT in percent recovery of developed pressure (58.99% +/- 4.8%, 51.54% +/- 3.5%, 53.09% +/- 3.2%, 66.43% +/- 7.3%, respectively) or compliance.nnnCONCLUSIONSnPin is as effective a cardioplegic agent as StT; however, its use as a pretreatment or additive to traditional and Pin in low potassium StT provided no additional benefit in functional recovery.

The superiority of pinacidil over adenosine cardioplegia in blood-perfused isolated hearts

BACKGROUNDnOur laboratory has shown that the potassium-channel opener pinacidil is an effective cardioplegic agent. A theoretical benefit of cardioplegia with potassium-channel openers is that it arrests the heart at hyperpolarized membrane potentials, a state of minimal metabolic requirement. This study was designed to examine another nondepolarizing agent, adenosine, and to test the hypothesis that it could provide comparable cardioprotection or augment potassium-channel opener cardioplegia.nnnMETHODSnUsing the blood-perfused Langendorff technique, isolated rabbit hearts were arrested for 30 minutes of global normothermic ischemia. Cardioplegia consisted of either Krebs-Henseleit solution alone (control) or with pinacidil (50 micromol/L), adenosine (200 micromol/L to 1 mmol/ L), or pinacidil + adenosine (200 micromol/L). Recovery of developed pressure and coronary flow were recorded.nnnRESULTSnPostischemic functional recovery for control, pinacidil, adenosine, and adenosine + pinacidil groups was 44.1%+/-3.4%, 59.5%+/-5.2% (p < 0.05 versus control), 37.0%+/-4.5%, and 56.0%+/-2.9%, respectively.nnnCONCLUSIONSnAdenosine, alone or as adjunct to pinacidil cardioplegia, was not an effective cardioplegic agent, despite shorter times to electromechanical arrest than control. The ineffectiveness of adenosine suggests that the cardioprotective properties of potassium-channel openers involve mechanisms other than the avoidance of membrane depolarization.

Cardioplegia-induced cell swelling: prevention by normothermic infusion

BACKGROUNDnPrevious work has shown significant swelling of isolated rabbit myocytes exposed to cold hyperkalemic cardioplegia; however, the effect of warm hyperkalemic cardioplegia on myocyte volume is unknown. This study examined the effect of warm hyperkalemic cardioplegia (St. Thomas solution) on myocyte volume.nnnMETHODSnMyocytes were enzymatically isolated and placed on an inverted video microscope. Tyrodes solution (37 degrees C) was infused for 10 minutes to establish baseline cell volumes. Subsequently, either the control Tyrodes or St. Thomas was infused either at 37 degrees C and 9 degrees C respectively (n = 5 for all groups) for 20 minutes, followed by a 30-minute reperfusion with 37 degrees C Tyrodes. Cell volume was determined from cell images captured every 5 minutes.nnnRESULTSnMyocyte swelling occurred rapidly on exposure to cold St. Thomas solution to a maximum of 9.8 +/- 2.1% (p < 0.001). In contrast, myocytes exposed to warm cardioplegia did not show any volume changes during exposure to cardioplegia. However, upon reexposure to Tyrodes, these cells showed shrinkage below their baseline volume (p < 0.001).nnnCONCLUSIONSnThe cell swelling associated with hypothermic cardioplegia is prevented by normothermic infusion.

Mechanisms responsible for cell volume regulation during hyperkalemic cardioplegic arrest

BACKGROUNDnCardioplegia has been shown to induce significant cell swelling. This study tested the hypothesis that (1) the [K+][Cl-] product of the cardioplegia solution is the main determinant of myocyte swelling, and (2) reperfusion myocyte shrinkage results from a rectifying Cl- conductance.nnnMETHODSnRabbit ventricular myocytes were superfused with 37 degrees C Krebs-Henseleit solution for 10 minutes. Then cells underwent 20 minutes of superfusion with standard St. Thomas solution ([K+][Cl-] product = 2566 mmol/L2) and two solutions with lower [K+][Cl-] product (1500 and 700 mmol/L2) at 9 degrees C. Cells were then resuperfused with 37 degrees C Krebs-Henseleit solution for 30 minutes. Cell volume was measured by videomicroscopy.nnnRESULTSnCells superfused with St. Thomas having [K+][Cl-] products of 2,566, 1,500, and 700 mmol/L2 swelled by 9.18%+/-3.57%, 5.51%+/-1.08%, and 1.49%+/-1.56%, respectively. Reexposure to Krebs-Henseleit solution caused these cells to shrink by 5.79%+/-1.41%, 8.72% +/-3.68%, and 13.46%+/-5.60%, respectively. This shrinkage was blocked by Cl- channel blockers given at the onset of superfusion.nnnCONCLUSIONSnLowering the [K+][Cl-] product of St. Thomas solution attenuated myocyte edema. Myocyte shrinkage during reexposure to Krebs-Henseleit solution resulted from the volume-activated Cl- channel.