Daniel Burkhoff

Histologic appearance of transmyocardial laser Channels after 41/2 Weeks

Preliminary results of clinical studies suggest that transmyocardial laser revascularization is an effective treatment for patients with chronic angina that cannot be treated by other means. The mechanism of this effect remains controversial. We present autopsy results from a patient obtained 4 1/2 weeks after operation that show that the channels do not maintain patency. Further work is needed to determine the frequency of channel patency and its relation to clinical benefit.

Histologic analysis of transmyocardial channels: comparison of CO2 and holmium:YAG lasers.

BACKGROUND Transmyocardial laser revascularization using different lasers is being tested in the treatment of refractory angina. We conducted comparative analysis of the acute and chronic myocardial effects of these different lasers. METHODS Transmyocardial channels were made in normal dog hearts with either a holmium:yttrium-aluminum garnet or a CO2 laser. Channels were examined histologically 6 to 24 hours, 2 to 3 weeks, and 6 weeks after creation. RESULTS Regardless of the laser source, the channels were occluded by thrombus within 6 to 24 hours. Subsequently, organization and neovascularization of the channel region occurred. Thermoacoustic damage was initially greater with the holmium:yttrium-aluminum garnet laser, but the channel appearances were indistinguishable from those made with the CO2 laser by 6 weeks. CONCLUSIONS Histologically, the myocardial effects of the CO2 and holmium:yttrium-aluminum garnet lasers are similar and differ predominantly in the amount of acute thermoacoustic injury. Channels are rapidly occluded by thrombus and are replaced by neovascularized collagen. This suggests that the physiologic effects of these two lasers may be similar and that mechanisms other than blood flow through chronic patent channels should be considered as contributing to the clinical benefits observed with this procedure.

Evidence of Vascular Growth Associated With Laser Treatment of Normal Canine Myocardium

BACKGROUND Transmyocardial laser revascularization is a new therapy for patients with refractory angina. Although clinical studies suggest that transmyocardial laser revascularization decreases angina and may improve regional blood flow, the underlying mechanisms are not elucidated. We hypothesized that one mechanism may relate to stimulation of vascular growth in laser-treated regions. METHODS Transmyocardial laser revascularization channels were made with holmium:yttrium-aluminum garnet or carbon dioxide lasers in eight normal canine hearts; animals were sacrificed 2 to 3 weeks later and examined for vascular density and for evidence of smooth muscle proliferation. RESULTS The original channels were infiltrated by granulation tissue with associated vascularity. Vascular growth was stimulated immediately surrounding the channel remnant as evidenced by an increase in the number of vessels (approximately twice that of the control region) and an increase in the number of vascular cells staining positive for markers of cellular proliferation. CONCLUSIONS Transmyocardial laser revascularization leads to local vascular growth as early as 2 weeks after treatment. It remains to be determined whether this mechanism contributes to increased regional blood flow or to clinical benefits associated with this novel form of therapy.

Inflow Valve Regurgitation During Left Ventricular Assist Device Support May Interfere With Reverse Ventricular Remodeling

BACKGROUND Left ventricular assist devices have been reported previously to reverse ventricular remodeling in patients with dilated cardiomyopathy. In patients with prolonged mechanical support, structural failure of the left ventricular assist device inflow valve can cause regurgitation into the left ventricle, which may affect adversely this process. METHODS Left ventricular end-diastolic pressure-volume relation of hearts explanted from 8 patients with left ventricular assist device and 8 control subjects with idiopathic cardiomyopathy was determined ex vivo at the time of transplantation. RESULTS Duration of mechanical support ranged from 210 to 276 days (mean +/- standard deviation = 283 +/- 76 days) in 3 patients with inflow valve regurgitation versus 100 to 155 days (132 +/- 22 days) in 5 patients without (p = 0.005). The end-diastolic pressure-volume relation of all hearts supported mechanically was shifted to the left toward normal controls. This effect was markedly attenuated in patients with inflow valve regurgitation. CONCLUSIONS Mechanical assistance can cause reverse remodeling in patients with dilated cardiomyopathy as evidenced by the shift in the end-diastolic pressure-volume relation curve to the left. Inflow valve failure, associated with prolonged support, can attenuate changes in left ventricular structure and dimension. Ineffective pressure and volume unloading may explain these observations.

Impact of isradipine on contractile performance, metabolism, and coronary resistance studied in isolated rat hearts.

In anesthetized dogs, isradipine has been reported to induce peripheral vasodilation and increase cardiac output (CO) and myocardial contractility, whereas myocardial oxygen consumption (MVO2) decreases, suggesting that isradipine may increase overall metabolic efficiency of the ventricle of intact animals. Whether isradipine has any direct myocardial effects that could cause intrinsic increase in metabolic efficiency or whether the observation relates to favorable isradipine-induced changes in hemodynamic loading conditions is not known. Therefore, we determined the direct myocardial effects of isradipine on contractile strength and metabolic efficiency in isolated rat heart. Isolated crystalloid perfused rat hearts were instrumented for measurement of ventricular pressure, volume, and MVO2. Isradipine decreased developed pressure (DP) and MVO2 in a concentration-dependent manner; at 32 nM irradipine, both quantities were approximately 70% of their control values. Isradipine caused a downward shift of the end-systolic pressure-volume relation (ESPVR) and in the relation between ventricular work (indexed by pressure-volume area, PVA) and MVO2, indicating that for any given amount of total mechanical work performed, the rat heart consumed less O2 during administration of isradipine than under control conditions. However, the magnitude of the downward shift of this relation was nearly identical to that observed in a separate group of hearts in which we decreased contractility by decreasing the perfusate calcium concentration. Thus, isradipine does not appear to have a contractility-independent effect on myocardial efficiency.