Retrograde Delivery Research Articles

Antegrade versus antegrade with retrograde delivery of cardioplegic solution in myocardial revascularisation. A clinical study in patients with triple vessel coronary artery disease.

The effects of antegrade and antegrade with retrograde delivery of cardioplegic solution were evaluated in 60 patients who underwent myocardial revascularisation. All patients had triple vessel coronary artery disease and underwent revascularisation using arterial and vein grafts. Myocardial protection consisted of administration of the St.Thomas' Hospital cardioplegic solution, topical slushed ice and systemic hypothermia (28 degrees C-30 degrees C). The patients were categorised into: group A (n=30), who received antegrade cardioplegia alone, and group B (n=30), who received antegrade and retrograde cardioplegia. With the exception of the total dose of cardioplegic solution ('p'=0.02), there was no significant difference between the two groups. Cardiac function was assessed before and after the patient was weaned from the cardio-pulmonary bypass. There was a significant increase in the right atrial pressure and a significant decrease in the mean arterial pressure from the baseline ('p'<0.05), 10 minutes after cardiopulmonary bypass in group A. All patients in-group B had a spontaneous return to sinus rhythm after release of the aortic cross clamp, whereas 3 patients in group A required defibrillation to restore sinus rhythm. Intra aortic balloon pump support was necessary in 4 patients in group A, as against 1 patient in group B to terminate the cardiopulmonary bypass. The clinical outcome was similar in both groups. We conclude that the use of a combination of retrograde and antegrade cardioplegia facilitates early recovery of left ventricular function after coronary artery bypass grafting.

Neurotrophic factor gene delivery supports axonal regeneration after injury

A successful treatment for spinal cord injury (SCI) must include means to induce axonal regeneration and synaptogenesis. Though much research has demonstrated the effectiveness of neurotrophic factors (NFs) in supporting axonal regeneration, systemic delivery of doses sufficient to reach therapeutic concentrations and overcome their short half‐lives has caused adverse effects. Local expression of NFs would overcome these limitations. We tested whether local expression of NFs would induce axonal regeneration without adverse effects in two models of neural injury. In a chemical injury model the rat serotonergic system was lesioned with p‐chloroamphetamine. When an adenoviral vector carrying the gene for brain‐derived neurotrophic factor (BDNF) was injected into the denervated cortex BDNF expressed by the transfected cells induced serotonergic axon reinnervation only in area around the injection site. In a mechanical injury model the cortical spinal tract (CST) in rats was lesioned unilaterally at the level of the hindbrain. Neurotorphin‐3 (NT‐3) was expressed locally in the spinal cord either by direct injection of an adenoviral vector carrying the gene for NT‐3 or by retrograde delivery of the vector from the sciatic nerve. Axons were observed growing from the unlesioned CST across the midline to the denervated side. These data demonstrate that local expression of NFs will induce and support axonal regeneration in a circumscribed area after injury without adverse effects and suggest that a therapy for SCI based upon this strategy may include NF gene delivery.Acknowledgements: Supported by NIH grant NS35280 and Mission Connect of the TIRR Foundation.

Efficient myocardial delivery of microspheres and endothelial cells via selective retrograde coronary venous delivery

Efficient myocardial delivery of microspheres and endothelial cells via selective retrograde coronary venous delivery

All-blood (miniplegia) versus dilute cardioplegia in experimental surgical revascularization of evolving infarction.

The advantages of blood cardioplegia include the oxygen-carrying capacity, superior oncotic and buffering properties, and endogenous antioxidants contained in blood. However, the partial dilution of blood in 4:1 (blood:crystalloid) cardioplegic solutions may nullify these advantages and progressively dilute blood during continuous retrograde delivery. This study tested the hypothesis that all-blood (66:1) cardioplegia provides superior myocardial protection compared with dilute (4:1) cardioplegia delivered in a continuous retrograde modality during surgical reperfusion of evolving myocardial infarction. After 60 minutes of left anterior descending coronary artery (LAD) occlusion, anesthetized canines were placed on cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group) or dilute blood cardioplegia (Dil group). After cross clamping, arrest was induced with 5 minutes of tepid (30 degrees C) antegrade potassium all-blood or dilute blood cardioplegia and maintained with tepid retrograde coronary sinus cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of arrest, simulating revascularization. The cardioplegia hematocrit for the Dil group was lower than that for the AB group (7+/-1% versus 12+/-2%, P<0.05); at the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab group (15+/-1% versus 20+/-1%, P<0.05). Infarct size (triphenyltetrazolium chloride staining) was comparable between the AB and Dil groups (29.6+/-2.9% versus 30.3+/-3.9% of area at risk), and there was no difference in area-at-risk myocardium systolic shortening (by sonomicrometry, -0.3+/-1% versus -0.4+/-1%). Tissue edema after bypass tended to be greater in the Dil group compared with the AB group in the heart (82+/-0% versus 81+/-1%), lung (79+/-1% versus 78+/-1%), liver (75+/-1% versus 74+/-0%), and skeletal muscle (76+/-1% versus 73+/-2%) and was significantly greater in the duodenum (80+/-1% versus 79+/-1%, P<0.05) and kidney (82+/-1% versus 79+/-1%, P<0.05). Postexperimental endothelial function (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil group (59+/-6% versus 77+/-5%, P<0.05). Both all-blood cardioplegia and dilute cardioplegia have disadvantages, but these do not have an impact on the pathogenesis of infarct size or recovery of regional contractile function.

All-Blood (Miniplegia) Versus Dilute Cardioplegia in Experimental Surgical Revascularization of Evolving Infarction

Background The advantages of blood cardioplegia include the oxygen-carrying capacity, superior oncotic and buffering properties, and endogenous antioxidants contained in blood. However, the partial dilution of blood in 4:1 (blood:crystalloid) cardioplegic solutions may nullify these advantages and progressively dilute blood during continuous retrograde delivery. This study tested the hypothesis that all-blood (66:1) cardioplegia provides superior myocardial protection compared with dilute (4:1) cardioplegia delivered in a continuous retrograde modality during surgical reperfusion of evolving myocardial infarction. Methods and Results After 60 minutes of left anterior descending coronary artery (LAD) occlusion, anesthetized canines were placed on cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group) or dilute blood cardioplegia (Dil group). After cross clamping, arrest was induced with 5 minutes of tepid (30°C) antegrade potassium all-blood or dilute blood cardioplegia and maintained with tepid retrograde coronary sinus cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of arrest, simulating revascularization. The cardioplegia hematocrit for the Dil group was lower than that for the AB group (7±1% versus 12±2%, P &lt;0.05); at the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab group (15±1% versus 20±1%, P &lt;0.05). Infarct size (triphenyltetrazolium chloride staining) was comparable between the AB and Dil groups (29.6±2.9% versus 30.3±3.9% of area at risk), and there was no difference in area-at-risk myocardium systolic shortening (by sonomicrometry, −0.3±1% versus −0.4±1%). Tissue edema after bypass tended to be greater in the Dil group compared with the AB group in the heart (82±0% versus 81±1%), lung (79±1% versus 78±1%), liver (75±1% versus 74±0%), and skeletal muscle (76±1% versus 73±2%) and was significantly greater in the duodenum (80±1% versus 79±1%, P &lt;0.05) and kidney (82±1% versus 79±1%, P &lt;0.05). Postexperimental endothelial function (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil group (59±6% versus 77±5%, P &lt;0.05). Conclusions Both all-blood cardioplegia and dilute cardioplegia have disadvantages, but these do not have an impact on the pathogenesis of infarct size or recovery of regional contractile function.

Repair Of Coronary Sinus Rupture Secondary To Internal Cardiac Massage

Injuries secondary to external and internal cardiac massage have been reported. This is the first report of coronary sinus injury secondary to internal cardiac massage. The technique used to repair the coronary sinus injury is described. INTRODUCTION Coronary Sinus Injury is a rare complication of the retrograde delivery of cardioplegia [1, 2]. This report describes coronary sinus injury secondary to internal cardiac massage and the technique used for repair. CASE REPORT A 68-year-old lady underwent coronary artery bypass graft surgery for triple vessel disease. The procedure was uneventful and during insertion of sternal wires, there was an unexplained drop in blood pressure followed by asystolic cardiac arrest. The wires were removed and internal cardiac massage was commenced. This was not particularly helpful and the patient was placed on cardiopulmonary bypass. The internal cardiac massage had caused injuries to the anterior surface of the heart (a small epicardial tear on the surface of the right ventricle) and the coronary sinus. There was a large amount of bleeding from the back of the heart and a large hematoma was present in the region of the coronary sinus. There was considerable venous bleeding from the sinus. The hematoma had obscured the tissue planes and it was not possible to discern clearly the edges of the defect in the coronary sinus all round (Figure 1). Figure 1 Figure 1: Coronary Sinus injury resulted in a large hematoma with obliteration of tissue planes. The edges of the coronary sinus injury were not discernible all round. The cross clamp was applied and the heart arrested with antegrade cardioplegia. The edges of the coronary sinus injury were not clearly defined. A large patch of pericardium (Tissuemed, Leeds, UK) was laid over the defect and sutured to the epicardial fat with Teflon (Bard Inc, Tempe, AZ) reinforced 40 prolene (Ethicon, Somerville, NJ) sutures. Bio glue (Cryolife, Kennesaw, GA) was then liberally applied at the edges of the pericardial patch (Figure 2). Figure 2 Figure 2: Repair of the coronary sinus injury by a pericardial patch sutured to the epicardial fat and secured by glue. The anterior epicardial tear was repaired with 40 prolene sutures. The cross clamp was removed and the patient was weaned off bypass uneventfully. The repair was intact and there was no further bleeding. The cause of the initial aystolic arrest Repair Of Coronary Sinus Rupture Secondary To Internal Cardiac Massage 2 of 3 was unexplained and the patient made an uneventful recovery. DISCUSSION Injuries secondary to internal and external cardiac massage have been reported [3]. Coronary sinus injury can occur secondary to cannulation for delivering retrograde cardioplegia [1,2]. To our knowledge, coronary sinus injury secondary to internal cardiac massage has not been reported. A ruptured coronary sinus is very difficult to repair primarily as the edges are not clearly seen and the hematoma causes obliteration of normal tissue planes. A large pericardial patch can be laid over the defect and sewn to the epicardial fat. This causes re-establishment of venous drainage. The application of glue to the edges of the pericardial patch helped secure a watertight repair and there was no further bleeding from the low-pressure venous system. We believe this technique of repair using a large pericardial patch sewn to the epicardial fat and secured by glue, makes it easy to manage a very difficult complication. CORRESPONDENCE TO Mr V Zamvar Tel : +44-(29)-20747747 Fax: +44-(29)-20745439 Email: zamvarv@hotmail.com Address: University Hospital of Wales, Cardiff CF14 4XW, UK

Retrograde flush perfusion with low-potassium solutions for improvement of experimental pulmonary preservation

Background Optimal preservation of post-ischemic organ function is a continuing challenge in clinical lung transplantation. Retrograde instillation of preservation solutions has the theoretic advantage of achieving homogeneous distribution in the lung because of perfusing both the pulmonary and the bronchial circulation. So far, we have seen no experimental studies that include stereologic analysis of intrapulmonary edema concerning the influence of retrograde preservation on post-ischemic lung function after preservation with Perfadex and Celsior. Methods In an extracorporeal rat model, we perfused 8 lungs, each, using either antegrade or retrograde perfusion technique with Celsior (CE ant/CE ret) and Perfadex (PER ant/PER ret). Results were compared with low-potassium Euro-Collins. Post-ischemic lungs were reventilated and reperfused mechanically. We continuously monitored relative oxygenation capacity (ROC), pulmonary artery pressure, flush time, and wet/dry ratio. Furthermore, we used stereologic means to evaluate edema formation. Statistics comprised different analysis of variance models. Results Relative oxygen capacity of CE ant-protected lungs was superior to that of PER ant preservation ( p = 0.05). Use of PER ret resulted in significantly higher ROC as compared with PER ant ( p < 0.001) and was comparable to results obtained with CE-preservation, which was not further improved with retrograde application. Conclusion Celsior provides better lung preservation than does Perfadex when administered antegradely. Retrograde application of Perfadex results in significant functional improvement as compared with antegrade perfusion, which reaches the standard of Celsior-protected organs. Additional in vivo experiments in combination with ultrastructural analysis are warranted to further evaluate retrograde delivery of preservation solutions, which could be used in clinical lung transplantation to further optimize current results.

Iaterogenic injuries during retrograde delivery of cardioplegia

During last eight years, retrograde delivery of cardioplegia was used on a regular basis, utilizing a DLP INC (Grand Rapids, MI) or a Research Medical INC (Salt Lake City UT) delivery systems, in almost an equal number of patients. This method resulted in a high pressure rupture, or perforation of the coronary sinus, its radicals or the right ventricle (RV) in 0.06% (5/7886) of patients. Intraoperative diagnosis of these injuries were confirmed on abnormal haemodynamic tracings and trans oesophageal echocardiography (TOE), and appearance of cardiac contusion or leakage of cardioplegia. A low incidence of these iaterogenic injuries may be attributed to: (1) a regular use of this method and (2) use of TOE guided manipulations in select high risk and reoperative patients. Repair of these injuries, as described, resulted in salvage of 4/5 (80%) patients.

Iaterogenic Injuries during Retrograde Delivery of Cardioplegia

During last eight years, retrograde delivery of cardioplegia was used on a regular basis, utilizing a DLP INC (Grand Rapids. MI) or a Research Medical INC (Salt Lake City UT) delivery systems, in almost an equal number of patients. This method resulted in a high pressure rupture, or perforation of the coronary sinus, its radicals or the right ventricle (RV) in 0.06% (5/7886) of patients. Intraoperative diagnosis of these injuries were confirmed on abnormal haemodynamic tracings and trans oesophageal echocardiography (TOE), and appearance of cardiac contusion or leakage of cardioplegia. A low incidence of these iaterogenic injuries may be attributed to: (1) a regular use of this method and (2) use of TOE guided manipulations in select high risk and reoperative patients. Repair of these injuries, as described, resulted in salvage of 4/5 (80%) patients.

Improved efficiency of gene transfer to the transplanted lung by retrograde vascular gene delivery

Abstract Experiments were designed to evaluate the efficiency of antegrade compared to retrograde vascular gene transfection of donor lungs used for transplantation. Rat donor lungs (n= 5/group) were transduced with an adenoviral vector encoding for β-galactosidase (AdβGal), either antegrade in the pulmonary artery (Group A, 3 ± 108 pfu, Group B, 3 ± 109 pfu) or retrograde into the pulmonary vein (Group C, 3 ± 108 pfu), immediately after pneumoplegia. After storage at 4 ±C for 1 h, the transduced lungs were transplanted orthotopically in syngeneic animals. The lungs were assessed for transgene expression by ELISA and X-Gal-staining at day 7 after operation. Inflammation was graded based on the extent of inflammatory cell infiltration. Transgene expression was similar between Groups A (1.7 ± 0.7 ng/mg protein) and B (2.1 ± 1.0 ng/mg protein). With retrograde delivery, there was a four-fold (8.3 ± 2.6 ng/mg protein) increase (P < 0.05) in transgene expression compared to either group A or B. In all groups, pneumocytes were transduced most frequently. The degree of inflammation correlated positively with the extent of transgene expression (r= 0.75, P < 0.01). The efficiency of vascular gene delivery to transplanted lungs can be improved by retrograde delivery of the vector via the pulmonary vein. Transgene expression predominates in pneumocytes following both antegrade and retrograde delivery. The severity of inflammation in the transplanted lung appears to correlate with the extent of transgene expression.

Gene therapy for ocular disease.

Gene therapy for ocular disease.

Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins.

Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication defective adenovirus within the targeted myocardium. Adenoviral vectors consisted either of luciferase (Ad.rsv-Luc) or beta-galactosidase (Ad.rsv-betaGal) reporter gene under control of an unspecific promotor derived from the Rous sarcoma virus (RSV). In this pig model, selective retrograde gene delivery into the anterior cardiac vein during a brief period of ischemia substantially increased reporter gene expression in the targeted myocardium (LAD region) compared with antegrade delivery as a control. Repeated retrograde delivery during two periods of brief ischemia resulted in a more homogeneous transmural expression predominantly observed in cardiomyocytes (X-gal-staining). In the nontargeted myocardium (CX region) there was no evidence for adenoviral transfection. From our data we infer that selective pressure-regulated retroinfusion is a promising approach for efficient percutaneous transluminal gene delivery to the myocardium. Gene Therapy (2000) 7, 232-240.

“I” ministernotomy for aortic valve replacement

Background. Minimally invasive surgical approaches have been applied recently in the management of valvular heart disease. In this report, we reviewed our preliminary experience of minimally invasive aortic valve replacement.Methods. Eighteen patients were operated on by means of an “I” ministernotomy, and 16 patients were operated on by means of a full median sternotomy during the same period. There was no difference between these two groups in term of age, sex, and preoperative left ventricular ejection fraction. In patients of the ministernotomy group, the operations were approached through an “I” median sternal split, from the second to the fifth intercostal space, 8 to 10 cm in length, with transverse division. Cardiopulmonary bypass was established through aorto–right atrial cannulation with aortic cross-clamping and antegrade or retrograde delivery of blood cardioplegia.Results. Under direct vision, aortic valve replacement was performed successfully in patients of both groups. The duration of cardiopulmonary bypass time and aortic cross-clamp time was significantly longer in the ministernotomy group than in the full sternotomy group. However, the length of incision, duration of endotracheal intubation, intensive care unit stay, pain score, postoperative length of stay, and return to normal activity interval were significantly shorter and lower in patients of the ministernotomy group than in those of the full sternotomy group. All patients recovered from the operation rapidly. Follow-up was complete in all patients with no late complications. Echocardiographic examination showed good function of aortic prostheses.Conclusions. Our experience demonstrates that the “I” ministernotomy provides good exposure, reduced wound pain, enhanced recovery, shortened hospital stay, and good cosmetic healing. It may be a good alternative for surgical correction of aortic valve lesions.

Influence of different routes of flush perfusion on the distribution of lung preservation solutions in parenchyma and airways.

The present study was performed to investigate the influence of different routes of perfusion on the distribution of the preservation solutions in the lung parenchyma and upper airways. Pigs were divided into four groups: control (n = 6), pulmonary artery (PA) (n = 6), simultaneous PA + bronchial artery (BA) (n = 8), and retrograde delivery (n = 6). After preparation and cannulation, cardioplegia solution and Euro-Collins solution (ECS) for lung preservation were given simultaneously. After removal of the heart, the double lung bloc was harvested. Following parameters were assessed: total and regional perfusion (dye-labeled microspheres), tissue water content, PA, aorta, left atrial and left ventricular pressures, cardiac output and lung temperature. Our data show that flow of the ECS in lung parenchyma did not reach control values (9.4+/-1.0 ml/min per g lung wet weight) regardless of the route of delivery (PA 6.3+/-1.5, PA + BA 4.8+/-0.9, retrograde 2.7+/-0.9 ml/min per g lung wet weight). However, flow in the proximal and distal trachea were significantly increased by PA + BA delivery (0.970+/-0.4, respectively, 0.380+/-0.2 ml/min per g) in comparison with PA (0.023+/-0.007, respectively, 0.024+/-0.070 ml/min per g), retrograde (0.009+/-0.003, respectively, 0.021+/-0.006 ml/min per g) and control experiments (0.125+/-0.0018, respectively, 0.105+/-0.012 ml/g per min). Similarly the highest flow rates in the right main bronchus were achieved by PA + BA delivery (1.04+/-0.4 ml/min per g) in comparison with 0.11+/-0.03 in control, 0.033+/-0.008 in PA, and 0.019+/-0.005 ml/min per g in retrograde group. Flows in the left main bronchus were 0.09+/-0.02 ml/min per g in control, 0.045+/-0.012 ml/min per g in PA, and 0.027+/-0.006 ml/min per g in retrograde group. The flow rates were significantly (P = 0.001) increased by PA + BA delivery of the storage solution (0.97+/-0.3 ml/min per g). Our data show that the distribution of ECS for lung preservation is significantly improved in airway tissues (trachea and bronchi) if a simultaneous PA + BA delivery is used.

Optimal flow rates for integrated cardioplegia

Background: Antegrade cardioplegic delivery may be impaired by coronary occlusions, whereas retrograde delivery of cardioplegic solution may be inhomogeneous, leading to an accumulation of lactate and hydrogen ions, the products of anaerobic metabolism. Integrated cardioplegia using continuous retrograde cardioplegia and antegrade infusions into completed vein grafts washes out metabolites accumulated in regions inadequately perfused by retrograde cardioplegia alone. To determine the flow rates required to achieve the greatest washout, we compared a high flow rate (200 ml/min) to a low flow rate (100 ml/min). Methods: Twenty patients scheduled for isolated coronary bypass surgery were prospectively randomized to compare two flow rates for integrated cardioplegic protection using tepid (29° C) blood cardioplegia. Arterial and coronary sinus blood samples were collected to evaluate myocardial metabolism. After antegrade arrest, cardioplegic solution was delivered by coronary sinus perfusion and simultaneous infusions into each completed vein graft at either high or low flow. Results: Increasing from low to high flow increased the washout of lactate and hydrogen ions during the aortic crossclamp period. Two hours after crossclamp removal, ventricular function was better in the high flow group. Conclusions: Tepid retrograde cardioplegia resulted in an accumulation of toxic metabolites. The addition of antegrade vein graft infusions at a flow rate of 100 ml/min resulted in a washout of these metabolites. A flow rate of 200 ml/min further improved this washout and resulted in improved ventricular function. An integrated approach to myocardial protection using a flow rate of 200 ml/min may improve the results of coronary bypass surgery. (J Thorac Cardiovasc Surg 1998;115:226–35)

Monitoring aortic root effluent during retrograde cardioplegia delivery.

Continuous monitoring of myocardial protection during aortic crossclamping is not always performed, due to limitations with current technology. The purpose of this study was to use readily available technology to evaluate the effectiveness of retrograde cardioplegia delivery by monitoring the aortic root vent effluent. The CDI 400, a commonly used blood monitoring device, was used to monitor changes in temperature, pO2, pCO2, and pH by placing a 1/4-inch CDI Quick Cell and probe in the aortic root vent line prior to each case. Twenty adult patients undergoing coronary bypass surgery were involved in the study, which resulted in 48 doses of retrograde cardioplegic solution. The study revealed a significant correlation between the temperature of the cardioplegia solution and the temperature of the aortic root effluent (p < 0.001. r = 0.88). The cardioplegia temperature did not correlate with the change in effluent pO2 (p = NS) or the degree of effluent temperature change (p = NS). Furthermore, the change in effluent temperature was not influenced by the amount of cardioplegia solution delivered (p = NS), or the time between administrations (p = NS). Both the decreasing and increasing trends of the effluent pO2 significantly correlated with the cardioplegia solution flow rate (p = 0.034, r = 0.32 and p = 0.013, r = 0.37, respectively), but not with the time between doses (p = NS) or volume of cardioplegia solution delivered (p = NS). The increase in effluent pO2 did correlate with the coronary sinus pressure (p < 0.001, r = 0.48). Measuring aortic root vent effluent may be used to assure the successful delivery of retrograde cardioplegic solution and aid in the detection of various procedural problems. Once the trends from this technique are established by the surgical team, they may be used to adjust cardioplegic solution administration and provide documentation of myocardial protection.

Assessment of retrograde cardioplegia with magnetic resonance imaging and localized 31p spectroscopy in isolated pig hearts

Objective: This study was done to determine whether retrograde delivery of cardioplegic solution provides uniform blood flow to the myocardium supplied by an occluded coronary artery and whether it maintains myocardial energy levels beyond the coronary occlusion. Methods: Isolated pig hearts were used. A hydraulic occluder was placed at the origin of the left anterior descending coronary artery. The perfusion pressure for retrograde delivery of cardioplegic solution was controlled at 40 to 50 mm Hg. Magnetic resonance imaging and localized 31P magnetic resonance spectroscopy were used to assess myocardial perfusion and energy metabolism, respectively. Results: Magnetic resonance perfusion images ( n = 7) showed that the perfusion defect that occurred during antegrade delivery of cardioplegic solution (as a result of the occlusion of the left anterior descending coronary artery) resolved during retrograde delivery of cardioplegic solution. Retrograde perfusion delivered similar amounts of flow to the jeopardized myocardium as it did to other areas of the myocardium. However, the distribution of cardioplegic solution by the retrograde route was heterogeneous (cloudlike) across both ventricular walls. 31P magnetic resonance spectra showed that the ischemic changes induced by occlusion of the left anterior descending artery during antegrade perfusion were greatly alleviated by retrograde perfusion; however, it took longer for retrograde cardioplegia ( n = 7, 17.08 minutes) to restore the levels of inorganic phosphate/phosphocreatine relative to the effect of releasing the left anterior descending artery occluder during antegrade delivery of cardioplegic solution ( n = 7, 5.3 minutes). Conclusions: First, retrograde delivery of cardioplegic solution provides sufficient flow to the myocardium beyond a coronary occlusion to maintain near normal levels of energy metabolites, and second, the efficacy of the retrograde route of cardioplegic solution delivery (in terms of distribution of the solution and rate of myocardial energy recovery) is significantly lower than that of the antegrade route(J Thorac Cardiovasc Surg 1997;114:109-116)

Port-access mitral valve replacement in dogs

Objective: The objective was to assess mitral valve replacement in a minimally invasive fashion by means of port-access technology. Methods: Fifteen dogs, 28 ± 3 kg (mean ± standard deviation), were studied with the port-access mitral valve replacement system (Heartport, Inc., Redwood City, Calif.). Eleven dogs underwent acute studies and were sacrificed immediately after the procedure. Four dogs were allowed to recover and then were sacrificed 4 weeks after operation. Cardiopulmonary bypass was conducted by femoral cannulation with an endovascular balloon catheter for aortic occlusion, root venting, and antegrade delivery of cardioplegic solution. Catheters were inserted in the jugular vein for pulmonary artery venting and retrograde delivery of cardioplegic solution. Through the oval port, a prosthesis (St. Jude Medical, Inc., St. Paul, Minn., or CarboMedics, Inc., Austin, Texas) was inserted through the left atrial appendage and secured to the anulus with sutures. Deairing was performed. Results: Cardiopulmonary bypass duration was 114 ± 24 minutes and aortic crossclamp time was 68 ± 14 minutes. All animals were weaned from cardiopulmonary bypass in sinus rhythm. Cardiac output and pulmonary artery occlusion pressure were unchanged (2.8 ± 0.7 L/min and 7 ± 3 mm Hg before operation vs 2.6 ± 0.6 L/min and 9 ± 4 mm Hg after operation). There was no mitral regurgitation according to left ventriculography in 13 of 15 dogs. In two dogs there was interference with prosthetic valve closure by residual native anterior leaflet tissue. Pathologic examination otherwise showed normal healing without perivalvular discontinuity. Microscopic studies showed no damage to the valve surfaces. Transthoracic echocardiography of the four dogs in the long-term study showed normal ventricular and prosthetic valve function 4 weeks after the operation. Conclusion: Mitral valve replacement with a minimally invasive method has been demonstrated in dogs. A clinical trial is in progress. (J T HORAC C ARDIOVASC S URG 1996;112:1268-74)

Adenovirus-mediated in vivo gene transfer and expression in normal rat pancreas.

Gene transfer into the pancreas would be useful for the treatment of a variety of disorders, including cystic fibrosis, diabetes, cancer, and immunomodulation of pancreatic allografts. A hypothesis that various cell populations in the pancreas could be targeted by recombinant adenoviruses was developed and tested. Gene transfer into the rat ductal epithelium, acinar cells, and islets of Langerhans was accomplished with a recombinant adenovirus containing bacterial beta-galactosidase by retrograde delivery of adenovirus into the pancreaticobiliary duct. Maximal gene expression was observed at 3 days and correlated with DNA blot analysis. Histologic analysis of sections from pancreatic tissue in the adenovirus-treated rats demonstrated severe pancreatitis. Immunophenotyping of the inflammatory infiltrate with rat lymphocyte-specific markers showed CD45-, CD8-, and CD4-positive cells. Tissue injury resolved as gene expression was lost, with both features absent by 21 days. Pancreatic regeneration was documented by the presence of 5-bromo-2'-deoxyuridine-positive staining cells. Pancreatic gene transfer with first-generation recombinant adenoviruses can be accomplished by techniques applicable to clinical situations. The use of first-generation recombinant adenoviruses for pancreas-directed gene transfer is limited by the development of inflammation and transient expression.

Can improved microvascular perfusion be achieved by using both antegrade and retrograde cardioplegia?

The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia. Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section). In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum. In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p < 0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.