The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assis... more The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assist device which provides diastolic augmentation and systolic unloading to the failing heart. It consists of a 60cc-pumping chamber, a percutaneous access device (PAD), and an external controller. The pumping chamber, is surgically implanted in the descending thoracic aorta with the patient on cardiopulmonary bypass. Its physiologic function is analogous to that of the intra-aortic balloon pump (IABP). Between 1997 and 2000, 5 men (age 59 to 73) with end-stage cardiomyopathy refractory to maximal drug treatment and with documented hemodynamic improvement on an IABP were enrolled in a feasibility study. Mean bypass time was 157 minute (range 120 to 196 minute); mean cross-clamp time was 101 minute (range 69 to 144). Patient 1 died intra-operatively. Compared with preoperative values, at 1 month, cardiac index increased (1.7 to 2.6 L/min/m(2)) and there were significant decreases in creatini...
We wanted to determine whether oxygen radicals open the mitochondrial ATP-dependent potassium cha... more We wanted to determine whether oxygen radicals open the mitochondrial ATP-dependent potassium channels (K(ATP)) during an ischemic period to reduce cell death and oxidant stress. Chick embryonic cardiomyocytes were used. Cell viability was quantified with propidium iodide (5 microM), and free radicals was measured using 2',7'-dichlorofluorescein diacetate. Preconditioning was produced by 10 min of simulated ischemia followed by 10 min of reoxygenation. Acetylcholine (1 mM), infused for 10 min instead of preconditioning, reduced cell death similarly (24 +/- 5%, n = 7 and 18 +/- 2%, n = 7, respectively, vs. controls, 49 +/- 6%, n = 8). In control series, 60 min of simulated ischemia and 3 h of reoxygenation generated free radicals more than 300% above the baseline (ischemia: 3.63 +/- 0.58, reoxygenation: 3.66 +/- 0.47, n = 8). Preconditioning and acetylcholine markedly attenuated the oxidant stress during simulated ischemia (1.18 +/- 0.41, n = 6 and 1.34 +/- 0.60, n = 7 vs. controls 3.63 +/- 0.58, n = 8) and re-oxygenation (1.23 +/- 0.36, n = 6 and 1.50 +/- 0.59, n = 7 vs. controls 3.66 +/- 0.47, n = 8). The protection of acetylcholine was abolished with pretreatment with the antioxidant thiol reductant 2-mercaptopropionyl glycine and posttreatment with 5-hydroxydecanoate, a selective mitochondrial K(ATP) channel antagonist (37 +/- 7%, n = 7). These results demonstrate that oxygen radicals open mitochondrial K(ATP) channels, which mediates the acetylcholine-induced preconditioning effect, and that stimulation of this signaling pathway attenuates oxidant stress.
Background. Vascular tissue remodels in response to a variety of hemodynamic factors, often trans... more Background. Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins.
Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Prot... more Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction. GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy. In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that [/R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration. These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.
The Journal of Heart and Lung Transplantation, 2000
Anastomotic Stenoses are well known as a complication of vascular and cardiovascular surgical pro... more Anastomotic Stenoses are well known as a complication of vascular and cardiovascular surgical procedures; such a lesion was encountered at the superior vena cava-right atrial anastomosis after cardiac transplantation. A balloon expandable stent was used to relieve this anastomotic constriction, employing a 16 mm diameter balloon to deliver a P304 stent. Stent placement resulted in complete relief of the patient's symptoms and facilitated the passage of bioptomes through the superior vena cava for subsequent biopsy procedures following cardiac transplantation. J Heart Lung Transplant 2000;19: 705-709.
The Journal of Heart and Lung Transplantation, 2003
Background: Traditionally leukocytes have been viewed as the mediators and effectors of cell inju... more Background: Traditionally leukocytes have been viewed as the mediators and effectors of cell injury after tissue ischemia and reperfusion through the indiscriminate release of toxic cytokines and oxygen free radicals. This can be detrimental to functioning of the transplanted heart when reperfused after implantation. Paradoxically, evidence now suggests that certain cytotoxic cytokines and even oxygen free radicals can be cytoprotective in smaller concentrations. This study sought to determine whether cultured human monocytes can be pre-conditioned by brief hypoxia to protect cardiomyocytes from cell death after hypoxia and re-oxygenation.
All rights reserved. No part of this publication may be reproduced in any form or by any electron... more All rights reserved. No part of this publication may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review.
Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scal... more Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scale renditions of the jets, which were difficult to differentiate from surrounding cardiac structures. Recently, a color-coded display of three-dimensional (3D) regurgitant flow has been developed. However, this display was unable to integrate cardiac anatomy, thereby losing spatial information, which made it difficult to determine the jet origin and its spatial trajectory. To overcome this limitation, an improved method of 3D color reconstruction of regurgitant jets obtained from color flow Doppler using a transesophageal approach was developed to allow the combined display of both color flow and gray scale information. To demonstrate the feasibility of 3D reconstruction of regurgitant mitral flow jets using an improved method of color encoding digital data acquired by transesophageal echocardiography (TEE). We studied 46 patients undergoing a clinically indicated TEE study. All subjects had mitral regurgitation detected on a previous transthoracic study. Atrial fibrillation or poor image quality were not used as exclusion criteria. The 3D study was performed using a commercial ultrasound imaging system with a TEE probe (Sonos 5500, Agilent Technologies). A rotational mode of acquisition was used to collect two-dimensional (2D) color flow images at 3-degree intervals over 180 degrees. Images were processed off line using the Echo-View Software (TomTec Imaging Systems). Volume-rendered 3D color flow jets were displayed along with gray scale information of the adjacent cardiac structures. Mitral regurgitant flow, displayed in left atrial and two longitudinal orientations, was successfully reconstructed in all patients. The time for acquisition, post-processing, and rendering ranged between 10 and 15 minutes. There were 28 centrally directed jets and 15 eccentric lesions. Eight patients in the study had periprosthetic mitral regurgitant flow. Three-dimensional imaging of mitral regurgitant jets is feasible in the majority of patients. This improved technique provides additional information to that obtained from the 2D examination. Particularly, in patients with paravalvular leaks 3D color flow Doppler provides information on the origin and the extent of the dehiscence, as well as insight into the jet direction. In addition, in patients with eccentric mitral regurgitation, this new modality overcomes the inherent limitations of 2D echo Doppler by depicting the full extent of the jet trajectory.
Intraoperative use of echocardiography is becoming more prevalent and is now considered an essent... more Intraoperative use of echocardiography is becoming more prevalent and is now considered an essential part of modern cardiac surgery. Echocardiography can be performed intraoperatively using transesophageal, epicardial or epiaortic, and substernal approaches. These techniques have a variety of applications in evaluating myocardial and valvular function, assessing aortic atheroma, and determining adequacy of various kinds of repair and reconstruction. Future applications will most likely involve more compact equipment, the implementation of epicardial and transesophageal real-time three-dimensional echocardiography, and better use of provocative methods of intraoperative testing.
The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assis... more The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assist device which provides diastolic augmentation and systolic unloading to the failing heart. It consists of a 60cc-pumping chamber, a percutaneous access device (PAD), and an external controller. The pumping chamber, is surgically implanted in the descending thoracic aorta with the patient on cardiopulmonary bypass. Its physiologic function is analogous to that of the intra-aortic balloon pump (IABP). Between 1997 and 2000, 5 men (age 59 to 73) with end-stage cardiomyopathy refractory to maximal drug treatment and with documented hemodynamic improvement on an IABP were enrolled in a feasibility study. Mean bypass time was 157 minute (range 120 to 196 minute); mean cross-clamp time was 101 minute (range 69 to 144). Patient 1 died intra-operatively. Compared with preoperative values, at 1 month, cardiac index increased (1.7 to 2.6 L/min/m(2)) and there were significant decreases in creatini...
We wanted to determine whether oxygen radicals open the mitochondrial ATP-dependent potassium cha... more We wanted to determine whether oxygen radicals open the mitochondrial ATP-dependent potassium channels (K(ATP)) during an ischemic period to reduce cell death and oxidant stress. Chick embryonic cardiomyocytes were used. Cell viability was quantified with propidium iodide (5 microM), and free radicals was measured using 2',7'-dichlorofluorescein diacetate. Preconditioning was produced by 10 min of simulated ischemia followed by 10 min of reoxygenation. Acetylcholine (1 mM), infused for 10 min instead of preconditioning, reduced cell death similarly (24 +/- 5%, n = 7 and 18 +/- 2%, n = 7, respectively, vs. controls, 49 +/- 6%, n = 8). In control series, 60 min of simulated ischemia and 3 h of reoxygenation generated free radicals more than 300% above the baseline (ischemia: 3.63 +/- 0.58, reoxygenation: 3.66 +/- 0.47, n = 8). Preconditioning and acetylcholine markedly attenuated the oxidant stress during simulated ischemia (1.18 +/- 0.41, n = 6 and 1.34 +/- 0.60, n = 7 vs. controls 3.63 +/- 0.58, n = 8) and re-oxygenation (1.23 +/- 0.36, n = 6 and 1.50 +/- 0.59, n = 7 vs. controls 3.66 +/- 0.47, n = 8). The protection of acetylcholine was abolished with pretreatment with the antioxidant thiol reductant 2-mercaptopropionyl glycine and posttreatment with 5-hydroxydecanoate, a selective mitochondrial K(ATP) channel antagonist (37 +/- 7%, n = 7). These results demonstrate that oxygen radicals open mitochondrial K(ATP) channels, which mediates the acetylcholine-induced preconditioning effect, and that stimulation of this signaling pathway attenuates oxidant stress.
Background. Vascular tissue remodels in response to a variety of hemodynamic factors, often trans... more Background. Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins.
Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Prot... more Myocardial ischemia and reperfusion (I/R) injury causes significant morbidity and mortality. Protection against I/R injury may occur via preservation of tissue metabolism and ATP content, preservation of reduced glutathione, and stimulation of heat shock protein (HSP) synthesis. Supplementation with glutamine (GLN) has been reported to have beneficial effects on all of these protective pathways. Thus, we hypothesized that GLN pretreatment given to the rat in vivo would protect the myocardium against I/R-induced dysfunction. GLN (0.52 g/kg, intraperitoneally, given as alanine-glutamine dipeptide), alanine alone (0.23 g/kg), or a Ringer's lactate solution (control) was administered to Sprague-Dawley rats 18 hours before heart excision, perfusion, exposure to global ischemia (15 minutes) and reperfusion (1 hour). Tissue metabolites were analyzed via magnetic resonance spectroscopy. In control and alanine-treated animals, I/R injury resulted in cardiac dysfunction, indicated by a decrease in cardiac output. Administration of GLN 18 hours before I/R injury preserved cardiac output after reperfusion. Metabolic analysis of the myocardial tissue revealed that [/R injury led to significant diminution of myocardial tissue glutamate, ATP content, accumulation of myocardial lactate, and a reduction in reduced glutathione content in control animals. GLN significantly reduced the deleterious changes in myocardial metabolism and improved reduced glutathione content. No changes in pre- or post-I/R injury HSP expression were observed after GLN administration. These observations demonstrate that remote in vivo administration of GLN before cardiac I/R injury can improve post-I/R cardiac function. This effect may be mediated via improved myocardial metabolism and enhanced reduced glutathione content.
The Journal of Heart and Lung Transplantation, 2000
Anastomotic Stenoses are well known as a complication of vascular and cardiovascular surgical pro... more Anastomotic Stenoses are well known as a complication of vascular and cardiovascular surgical procedures; such a lesion was encountered at the superior vena cava-right atrial anastomosis after cardiac transplantation. A balloon expandable stent was used to relieve this anastomotic constriction, employing a 16 mm diameter balloon to deliver a P304 stent. Stent placement resulted in complete relief of the patient's symptoms and facilitated the passage of bioptomes through the superior vena cava for subsequent biopsy procedures following cardiac transplantation. J Heart Lung Transplant 2000;19: 705-709.
The Journal of Heart and Lung Transplantation, 2003
Background: Traditionally leukocytes have been viewed as the mediators and effectors of cell inju... more Background: Traditionally leukocytes have been viewed as the mediators and effectors of cell injury after tissue ischemia and reperfusion through the indiscriminate release of toxic cytokines and oxygen free radicals. This can be detrimental to functioning of the transplanted heart when reperfused after implantation. Paradoxically, evidence now suggests that certain cytotoxic cytokines and even oxygen free radicals can be cytoprotective in smaller concentrations. This study sought to determine whether cultured human monocytes can be pre-conditioned by brief hypoxia to protect cardiomyocytes from cell death after hypoxia and re-oxygenation.
All rights reserved. No part of this publication may be reproduced in any form or by any electron... more All rights reserved. No part of this publication may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review.
Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scal... more Prior studies have reconstructed mitral regurgitant flow in three dimensions displaying gray scale renditions of the jets, which were difficult to differentiate from surrounding cardiac structures. Recently, a color-coded display of three-dimensional (3D) regurgitant flow has been developed. However, this display was unable to integrate cardiac anatomy, thereby losing spatial information, which made it difficult to determine the jet origin and its spatial trajectory. To overcome this limitation, an improved method of 3D color reconstruction of regurgitant jets obtained from color flow Doppler using a transesophageal approach was developed to allow the combined display of both color flow and gray scale information. To demonstrate the feasibility of 3D reconstruction of regurgitant mitral flow jets using an improved method of color encoding digital data acquired by transesophageal echocardiography (TEE). We studied 46 patients undergoing a clinically indicated TEE study. All subjects had mitral regurgitation detected on a previous transthoracic study. Atrial fibrillation or poor image quality were not used as exclusion criteria. The 3D study was performed using a commercial ultrasound imaging system with a TEE probe (Sonos 5500, Agilent Technologies). A rotational mode of acquisition was used to collect two-dimensional (2D) color flow images at 3-degree intervals over 180 degrees. Images were processed off line using the Echo-View Software (TomTec Imaging Systems). Volume-rendered 3D color flow jets were displayed along with gray scale information of the adjacent cardiac structures. Mitral regurgitant flow, displayed in left atrial and two longitudinal orientations, was successfully reconstructed in all patients. The time for acquisition, post-processing, and rendering ranged between 10 and 15 minutes. There were 28 centrally directed jets and 15 eccentric lesions. Eight patients in the study had periprosthetic mitral regurgitant flow. Three-dimensional imaging of mitral regurgitant jets is feasible in the majority of patients. This improved technique provides additional information to that obtained from the 2D examination. Particularly, in patients with paravalvular leaks 3D color flow Doppler provides information on the origin and the extent of the dehiscence, as well as insight into the jet direction. In addition, in patients with eccentric mitral regurgitation, this new modality overcomes the inherent limitations of 2D echo Doppler by depicting the full extent of the jet trajectory.
Intraoperative use of echocardiography is becoming more prevalent and is now considered an essent... more Intraoperative use of echocardiography is becoming more prevalent and is now considered an essential part of modern cardiac surgery. Echocardiography can be performed intraoperatively using transesophageal, epicardial or epiaortic, and substernal approaches. These techniques have a variety of applications in evaluating myocardial and valvular function, assessing aortic atheroma, and determining adequacy of various kinds of repair and reconstruction. Future applications will most likely involve more compact equipment, the implementation of epicardial and transesophageal real-time three-dimensional echocardiography, and better use of provocative methods of intraoperative testing.
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