Shankha S Biswas

Induction of angiogenesis after TMR: a comparison of holmium: YAG, CO2, and excimer lasers.

BACKGROUND Transmyocardial laser revascularization (TMR) is an emerging treatment for end-stage coronary artery disease. A variety of lasers are currently available to perform the procedure, although their relative efficacy is unknown. The purpose of this study was to compare changes in myocardial blood flow and function 6 months after TMR with holmium:yttrium-aluminum-garnet (holmium:YAG), carbon dioxide (CO2), and xenon chloride excimer lasers in a model of chronic ischemia. METHODS Miniswine underwent subtotal (90%) left circumflex coronary stenosis. Baseline positron emission tomography and dobutamine stress echocardiography were performed to document hibernating myocardium in the left circumflex coronary artery distribution. Animals were then randomized to sham redo-thoracotomy (n = 5) or TMR using a holmium:YAG (n = 5), CO2 (n = 5) or excimer (n = 5) laser. Six months postoperatively, the positron emission tomography and dobutamine stress echocardiography studies were repeated and the animals sacrificed. RESULTS In animals undergoing TMR with holmium: YAG and CO2 lasers, a significant improvement in myocardial blood flow to the lased left circumflex regions was seen. No significant change in myocardial blood flow was seen in sham- or excimer-lased animals. There was a significant improvement in regional stress function of the lased segments 6 months postoperatively in animals undergoing holmium:YAG and CO2 laser TMR that was consistent with a reduction in ischemia. There was no change in wall motion in sham- or excimer-lased animals. Significantly greater neovascularization was observed in the holmium:YAG and CO2 lased regions than with either the sham procedure or excimer TMR. CONCLUSIONS Transmyocardial laser revascularization with either holmium:YAG or CO2 laser improves myocardial blood flow and contractile reserve in lased regions 6 months postoperatively. These changes were not seen following excimer TMR or sham thoracotomy, suggesting that differences in laser energy or wavelength or both may be important in the induction of angiogenesis.

Right ventricular dysfunction after cardiac transplantation: primarily related to status of donor heart

BACKGROUND It is unclear whether right ventricular dysfunction after transplantation is due to donor brain death-related myocardial injury or recipient pulmonary hypertension. METHODS A canine donor model of brain death and a monocrotaline pyrrole-induced chronic pulmonary hypertension recipient model were established, and used for 30 orthotopic bicaval cardiac transplantations divided into three groups: Controls (group A, normal donor/recipient), group B (brain-dead donors/normal recipient), and group C (normal donor/recipients with pulmonary hypertension). Right ventricular function was measured before transplant and brain death, 4 hours after brain death, and after transplant (1 hour off bypass) by load-independent means plotting stroke work versus end-diastolic volume during caval occlusion. Right ventricular total power and pulmonary vascular impedance were determined by Fourier analysis. RESULTS In comparison to the control group right ventricular preload-recruitable stroke work and total power decreased significantly after brain death and transplant in group B (from 22.7 x 10(3) erg (+/-1.2) at baseline to 15.6 x 10(3) (+/-0.9) after brain death and to 11.3 x 10(3) (+/-0.9) after transplant). In group C there was a significant increase in pulmonary artery pressure, impedance, right ventricular preload-recruitable stroke work, total power after transplant. CONCLUSIONS Normal donor hearts adapt acutely to the recipients elevated pulmonary vascular resistance by increasing right ventricular power output and contractility. Brain death caused significant right ventricular dysfunction and power loss, which further deteriorated after graft preservation and transplantation. The effects of donor brain death on myocardial function contribute to right ventricular dysfunction after cardiac transplantation.

Histological Evidence of Angiogenesis 9 Months After Transmyocardial Laser Revascularization

A 66-year-old white male with end-stage ischemic cardiomyopathy was referred to our center for transmyocardial laser revascularization (PLC Eclipse Surgical Technologies) in July 1999. The patient had a long history of interventions for his coronary artery disease, including multiple percutaneous transluminal coronary angioplasties, stent placement in 1991 and 1993, and coronary artery bypass grafting in 1987 and 1992. He was evaluated for a third bypass, but we determined he was not a suitable candidate because of his diffuse small vessel distal coronary artery disease. Given the limitations of conventional therapeutic options, the patient underwent transmyocardial laser revascularization in July 1999. Thirty transmural channels were lased in the ischemic anterior and lateral walls of the left ventricle. The patient tolerated the procedure well and received anginal relief for the following 6 months; he then experienced recurrent symptoms …

A Comparison of Mechanical and Laser Transmyocardial Revascularization for Induction of Angiogenesis and Arteriogenesis in Chronically Ischemic Myocardium

OBJECTIVES The purpose of the present study was to compare the use of a mechanical transmyocardial implant (TMI) device with transmyocardial laser revascularization (TMR) for induction of therapeutic angiogenesis and arteriogenesis in the chronically ischemic heart. BACKGROUND Prior experimental studies have demonstrated evidence for neovascularization after both mechanical and laser transmyocardial revascularization, although a long-term comparison of the two techniques has not been performed. METHODS Using an established model of chronic hibernating myocardium, mini-swine underwent 90% proximal left circumflex (LCx) coronary artery stenosis. One month later, baseline positron emission tomography (PET) and dobutamine stress echocardiography (DSE) were performed to quantitate regional myocardial blood flow (MBF) and function. Animals then underwent TMR with a holmium:yttrium-aluminum-garnet (holmium:YAG) laser (n = 5), TMI (n = 5), or sham redo-thoracotomy (n = 5). In the TMR group, the entire LCx region was treated with transmural laser channels at a density of 1/cm(2). Transmyocardial implants were placed transmurally at a similar density in the LCx region of the TMI group. Six months later, the PET and DSE studies were repeated, and the animals were euthanized. RESULTS Six months after TMR, there was a significant increase over baseline in resting MBF to the lased LCx region (68.9 +/- 4.6% vs. 89.3 +/- 3.0% reference non-ischemic septal segments; p < 0.001). This increased MBF was accompanied by a significant improvement in LCx regional wall motion during peak dobutamine stress (p = 0.04). Compared with baseline, there was no change in LCx region MBF six months after either TMI (72.9 +/- 4.8% vs. 85.7 +/- 3.4%; p = 0.10) or sham redo-thoracotomy (75.6 +/- 4.6% vs. 80.1 +/- 5.0%; p > 0.2). Likewise, there was no significant change in rest or stress wall motion by DSE six months postoperatively in either group. Overall vascular density was increased only in the TMR-treated regions six months postoperatively. The difference between groups was most notable for a twofold increase in the number of small arterioles seen in the lased (4.4 +/- 0.3 arterioles per high power field; p < 0.001 vs. both TMI and sham) compared with TMI (2.2 +/- 0.2) and sham (1.9 +/- 0.2)-treated regions. CONCLUSIONS Mechanical transmyocardial revascularization with a TMI device does not appear to promote physiologically significant angiogenesis or arteriogenesis in the chronically ischemic porcine heart and cannot be recommended for clinical trials at this time. Infrared laser-mediated injury mechanisms may be important for inducing therapeutic neovascularization with direct myocardial revascularization techniques.

Brain Death Further Promotes Ischemic Reperfusion Injury of the Rabbit Myocardium

BACKGROUND Little is known about preload-dependent cardiac function after brain death (BD) and subsequent graft preservation. METHODS A validated model of BD in rabbits was developed and myocardial performance was studied after BD induction and 1 hour of subsequent global hypothermic ischemia using a validated rabbit model and an isolated work-performing heart preparation. RESULTS Significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed 2 hours after BD. After global hypothermic ischemia, significant decreases in stroke work, left ventricular contractility, and left ventricular relaxation were observed in the BD group compared with controls. Cardiac output and coronary flow were also significantly decreased in BD hearts compared with controls. Creatine kinase release was increased by 32.5% in BD hearts compared with controls. CONCLUSIONS In a rabbit model, BD combined with global hypothermic ischemia causes a significant decrease in left ventricular function compared with global hypothermic ischemia. This dysfunction may be attributed to a significant decrease in coronary flows in BD hearts.

Changes in systolic and diastolic function during multivessel off-pump coronary bypass grafting

OBJECTIVE To measure the changes in systolic and diastolic left ventricular function that occur during off-pump coronary artery bypass grafting (OPCAB) as a consequence of positioning the heart and interrupting coronary flow. METHODS 2-D Transoesophageal echocardiography was used to derive systolic wall motion indices and pulsed Doppler parameters of diastolic function including the E/A ratio, PVS/PVD ratio, and deceleration time. A continuous cardiac output thermodilution pulmonary artery catheter was used to provide hemodynamic measures of left ventricular function. Data was obtained prior to, during and following coronary grafting. RESULTS Thirty-four consecutive anastomoses were evaluated, including eight circumflex (LCX), 17 left anterior descending artery (LAD) and nine right coronary artery (RCA) anastamoses. Significant changes in diastolic and systolic cardiac function were identified in those patients who underwent LCX grafting. Specifically during LCX grafting, both wall motion score index (2.4+/-1.4 vs 1.5+/-0.63 and 1.9+/-0.91) and the E/A ratio were significantly increased (3.5+/-1.4 vs 1.1+/-0.33 and 1.2+/-0.44) when compared to RCA and LAD grafting, respectively. The PVS/PVD ratio was significantly decreased during left circumflex grafting (0.7+/-0.45 vs 1.1+/-0.19 and 1.0+/-0.58) when compared to RCA and LAD grafting, respectively. All functional parameters returned to baseline by the end of surgery. CONCLUSIONS Multivessel OPCAB can be achieved with mild impairment of left ventricular function that returns to baseline by the end of the procedure. Impairment of diastolic function is most marked during circumflex grafting as demonstrated by a restrictive filling pattern. Measures of diastolic function may be helpful in developing better strategies for exposure of the circumflex graft site.

Regional cardiac sympathetic innervation early and late after transmyocardial laser revascularization.

Abstract  Background. Prior experimental and clinical studies have drawn disparate conclusions regarding the effects of transmyocardial laser revascularization (TMR) on regional cardiac innervation in the treated regions. Regional afferent denervation has been proposed as a potential mechanism of action of the procedure, although this as yet remains unproven. The purpose of the present study was to evaluate regional myocardial sympathetic innervation both early (3 days) and late (6 months) after TMR. Methods. Mini‐swine in the early group were randomized to be sacrificed 3 days after holmium:YAG TMR (n = 5) or sham thoractomy (n = 3). In the late group, mini‐swine with hibernating myocardium in the left circumflex (LCx) region were randomized to sham redo‐thoracotomy (n = 5), TMR of the LCx distribution with a carbon dioxide (n = 5), holmium:YAG (n = 5), or excimer (n = 5) laser. Six months postoperatively the animals were sacrificed. Additional animals in both the early (n = 2) and late (n = 2) groups served as age‐ and weight‐matched normal controls. Immunohistochemistry and Western blot analysis for tyrosine hydroxylase (TYR‐OH), a neural‐specific enzyme found in sympathetic efferent nerves and a commonly used anatomic marker of regional innervation, were performed on lased and nonlased LCx and septal regions. Results. Immunohistochemical staining for TYR‐OH was markedly diminished in the lased myocardial regions 3 days after TMR. This staining was significantly reduced compared to untreated septal regions, sham‐operated, and normal LCx myocardium. Quantitative immunoblotting confirmed a significant reduction in TYR‐OH (p < 0.05) protein concentration in the lased regions 3 days after TMR. On the contrary, TYR‐OH staining was present in LCx myocardium surrounding the laser channels of all animals in all groups 6 months postoperatively. Staining was not different from controls. Similarly, there was no difference in LCx TYR‐OH protein concentration between the normal, sham, or 6 months postoperative lased groups (p > 0.2 by one‐way ANOVA). Conclusions. TMR‐treated myocardium demonstrates anatomic evidence of regional sympathetic denervation 3 days postoperatively, although myocardium lased with each of the three lasers currently in clinical use is reinnervated by 6 months as evidenced by immunoblotting and immunohistochemistry for TYR‐OH. These results suggest that mechanisms other than denervation may account for the long‐term reductions in angina seen after TMR. (J Card Surg 2004;19:21‐27)

Non–Blood-Contacting Biventricular Support: Direct Mechanical Ventricular Actuation

The concept of nierlianicall~ conipr ing the ventrirles of a failing heart into a sy stolic cwnfiguration followed I)! pa5sive or mechanicall\. assisted diastole is not new. 4 variety of bellows. wrap-around devices, antl cups have lteen prOl~’5t3etl t o angment forward cardiac flow after cardiac arrest. For example, 27 patents have Iieen issued in the United States alone for a Fariety of such tlevices 1)eginning as early as 1936. Although seemingly simple antl elegant , no one has yet to qufficiently stud) and refine this concept to pi-oduce an accepted. commercially available means to support the failing circulation. In fact, the overwhelming majority of patents issued were for totally unassemhled antl untested devices. Direct mechanical ventricular actuation (DMVA), as deeloped to date in our laboratory, is the only non-hloodcontacting means to achieve rapid, biventricular circulatory support.’ l’ D y n amic cardiomyoplasty using blood-contacting latissimus dorsi muscle requires weeks of muscle preconditioning before transfer around the heart and provides only limited assistance in its present state of development antl has largely been abandoned. Non-blood-contacting biventricular support using DMVA has the following advantages:

Robotically assisted versus conventional freehand technique during beating heart anastomoses of left internal thoracic artery to left anterior descending artery

BACKGROUND Although robotically assisted coronary arterial anastomoses are being performed clinically, the short-term and long-term quality and integrity of the left internal thoracic artery (LITA) to left anterior descending artery (LAD) anastomosis remains unknown. The goal of this study was to perform a histologic and angiographic assessment of porcine beating heart LITA to LAD anastomoses using either robotic assistance or a conventional freehand technique. METHODS Twelve pigs underwent beating heart LITA to LAD anastomoses using either the robotically assisted (n = 6) or conventional freehand techniques (n = 6). Quantitative histologic analysis was performed in all animals in order to determine the degree of vascular wall damage. Selective coronary arteriography was performed in all animals immediately after the procedure in order to evaluate anastomotic patency. The unpaired Students t test was used for all comparisons between groups. RESULTS There were no differences in vascular wall damage between the robotically assisted and freehand techniques. Postoperative angiography revealed no stenoses in either group. CONCLUSIONS Use of the robotically assisted technique for creation of a LITA to LAD anastomosis was not associated with increased histologic damage when compared with the freehand technique in a beating heart porcine model. Furthermore, there was no difference between the two techniques in postoperative patency rate. These results support further clinical investigation of robotically assisted coronary bypass surgery.

Valve replacement for appetite suppressant-induced valvular heart disease.

Valvular heart disease associated with the use of appetite-suppressant medication is a recently described clinical entity. Although the mechanism of valvular injury remains elusive pathologically, the valvular abnormalities resemble those observed in carcinoid syndrome. The incidence of clinically evident valvular heart disease is low with short-term (less than 3 months) exposure to appetite-suppressant drugs. Prolonged exposure to higher doses in addition to combination drug therapy confers an excess risk for valvular pathologic changes. We report the case of a patient with severe mitral regurgitation who had short-term exposure (3 weeks) to the combination of fenfluramine (20 mg) and phenteramine (15 mg).