Quantitation of the critically ischemic zone at risk during acute coronary occlusion using PET.

Critical myocardial ischemia has been defined experimentally during acute coronary occlusion as flow reduction of 50% or more since cellular ATP depletion begins to occur beyond this flow reduction threshold, placing tissue at risk of cellular injury. To test the hypothesis that critically ischemic fractional left ventricular mass can be measured noninvasively with PET, nine dogs were imaged in a multi-slice positron camera using the perfusion tracer 13N-ammonia, while radiolabeled microspheres were injected into the left atrium during acute coronary occlusion. Images were processed using a 50% threshold and the size of the resulting perfusion defect was expressed as a fraction of total left ventricular image volume. The critically ischemic left ventricular fraction determined in vitro from the microsphere perfusion data, ranged from 5% to 30% of the total left ventricular weight and correlated closely with that determined noninvasively by PET with r = 0.94 (y = 1.05X - 2.0%). We conclude that the fraction of left ventricular myocardium rendered critically ischemic during acute coronary occlusion can be measured accurately and noninvasively in vivo using perfusion imaging with positron emission tomography.

Improved infarct-related arterial patency after high dose, weight-adjusted, rapid infusion of tissue-type plasminogen activator in myocardial infarction: results of a multicenter randomized trial of two dosage regimens.

To determine whether a weight-adjusted high dose (2 mg/kg body weight over 3 h) rapid infusion of recombinant tissue-type plasminogen activator (rt-PA) was more efficacious than a weight-adjusted standard dose (1.25 mg/kg over 3 h) in achieving reperfusion in the setting of acute myocardial infarction, 175 patients were entered into a randomized multicenter trial. Eighty-four patients were entered into the high dose group, receiving 1.2 mg/kg (10% given as a bolus injection) over 1 h, followed by 0.8 mg/kg over the next 2 h. Ninety-one patients were given 0.75 mg/kg (10% given as a bolus injection) in 1 h, followed by 0.5 mg/kg administered over the next 2 h. The median dose in the group that received 2 mg/kg dose was 145 mg, compared with 100 mg in the group that received 1.25 mg/kg. The 90 min patency rate in the group that received 2 mg/kg was 84% compared with 70% in the group that received 1.25 mg/kg (p = 0.003). Sixty-four percent of the patients in each group underwent coronary angioplasty at the time of cardiac catheterization. The infarct-related artery patency rate at the end of catheterization was 91% in the group that received 2 mg/kg compared with 83% in the group that received 1.25 mg/kg (p = 0.08). Among patients with a patent infarct-related coronary artery after catheterization, the 6 month mortality rate in the group that received 2 mg/kg was 2.9% compared with 9.8% in the group that received 1.25 mg/kg (p = 0.15). The bleeding complication rate in the two groups was similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the hemopump left ventricular assist device on regional myocardial perfusion and function. Reduction of ischemia during coronary occlusion.

The Hemopump is a new 7-mm diameter left ventricular assist device that provides as much as 3.5 l/min of nonpulsatile cardiac output after fluoroscopic placement into the left ventricle through a femoral artery cutdown. The purpose of this study was to measure the effects of Hemopump assist on hemodynamics, left ventricular function, and perfusion in the presence and absence of ischemia. Eight dogs were instrumented under pentobarbital anesthesia with left ventricular, left atrial, and aortic catheters, a loose silk ligature around the midleft anterior descending coronary artery, and sonomicrometer crystals in midwall myocardium within the left anterior descending and circumflex perfusion territories. Hemodynamic variables, regional systolic fractional shortening, and myocardial perfusion after left atrial injection of 15-microns radiolabeled microspheres were measured in the presence and absence of Hemopump assist before and after left anterior descending artery occlusion. In the absence of ischemia, Hemopump left ventricular assist resulted in reduced left ventricular end-diastolic pressure while aortic mean pressure was maintained, and there was significant reduction in regional systolic fractional shortening (reflecting systolic unloading) that correlated with an 18% decline in regional myocardial perfusion. During left anterior descending artery occlusion, left ventricular systolic and diastolic pressures were reduced during Hemopump assist while aortic mean pressure was maintained. Perfusion rose in the ischemic territory (from 13.0 +/- 8.7% to 26.2 +/- 19.8% of nonischemic flow, p = 0.045). Reduced fractional shortening was again seen in nonischemic tissue with Hemopump assist during left anterior descending artery occlusion, and this was often correlated with reduced perfusion (r = 0.67).(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of coronary artery disease severity by positron emission tomography. Comparison with quantitative arteriography in 193 patients.

To assess the accuracy of positron emission tomography (PET) for evaluation of coronary artery disease (CAD), cardiac PET perfusion images were obtained at rest and with dipyridamole-handgrip stress in 193 patients undergoing coronary arteriography. PET images were reviewed by two independent readers blinded to clinical data. Subjective defect severity scores were assigned to each myocardial region on a 0 (normal) to 5 (severe) scale. Results were compared with arteriographic stenosis severity expressed as stenosis flow reserve (SFR), with continuous values ranging from 0 (total occlusion) to 5 (normal), calculated from quantitative arteriographic dimensions using automated detection of the vessel borders. There were 115 patients with significant CAD (SFR less than 3), 37 patients with mild CAD (3 less than or equal to SFR less than 4), and 41 patients with essentially normal coronaries (SFR greater than or equal to 4). With increasingly severe impairment of stenosis flow reserve, subjective PET defect severity increased. Despite wide scatter, a PET score of 2 or more was highly predictive of significant flow reserve impairment (SFR less than 3). For each patient, the score of the most severe PET defect correlated with the SFR of that patient's most severe stenosis (rs = 0.77 +/- 0.06). For each of 243 stenoses, PET defect score correlated with the SFR of the corresponding artery (rs = 0.63 +/- 0.08). PET defect location closely matched the region supplied by the diseased artery, and readers agreed whether the most severe PET defect was less than or more than 2 for 89% of patients.

Catecholamine stimulation, substrate competition, and myocardial glucose uptake in conscious dogs assessed with positron emission tomography.

Uptake of radiolabelled deoxyglucose out of proportion to reduced coronary flow demonstrated by positron emission tomography has been used to identify reversibly ischemic, viable myocardium. For this concept to be applied reliably in the clinical setting, factors that may depress glucose availability independent of tissue viability, such as adrenergic stimulation and substrate competition, must be examined. Accordingly, we studied the effect of catecholamine stimulation by dopamine on myocardial glucose uptake in vivo using chronically instrumented, intact dogs and positron emission tomography. We measured myocardial activity of [2-18F]-2-deoxyglucose (FDG) and 82Rb in glucose-loaded animals randomly studied during dopamine infusion, during insulin infusion, and then during their combined infusion. Myocardial FDG uptake was significantly decreased when animals were treated with dopamine, compared with treatment in the same animals with insulin. When insulin was added to the dopamine infusion, myocardial FDG uptake was restored. In contrast, myocardial activity of 82Rb, which is taken up in proportion to coronary flow, was similar under all three experimental conditions. Plasma glucose, free fatty acid, and lactate concentrations were determined before and during each infusion. The depression of myocardial FDG activity seen during dopamine infusion and its reversal with addition of insulin can be explained on the basis of effects of these hormones on substrate availability and competition.

Changes in myocardial perfusion reserve after PTCA: noninvasive assessment with positron tomography.

The effect of percutaneous transluminal coronary angioplasty (PTCA) on myocardial perfusion reserve has not been previously determined. Accordingly, 11 patients underwent positron imaging with [13N]ammonia or 82Rb at rest and following dipyridamole + handgrip stress before and after PTCA. The ratio of stress to rest activity (S:R) was determined for each region of interest. Relative myocardial perfusion reserve by positron tomography (RMPR) was calculated by dividing S:R of the stenotic area by a corresponding value from a normal reference area of the same patient. Automated quantitative coronary arteriography was used to objectively measure the percent diameter (%D) and the percent area narrowing (%A) of the stenoses. In nine patients with successful PTCA, %D and %A improved (68 +/- 10 to 49 +/- 15% and 92 +/- 3 to 72 +/- 5%) and RMPR increased from 0.79 +/- 0.07 to 0.96 +/- 0.05. In the two patients in whom PTCA was unsuccessful, RMPR was unchanged. Changes in RMPR correlated inversely with changes in %D (r = -0.68) and %A (r = -0.92) and directly with improved coronary flow reserve derived from all stenosis measurements (r = 0.73, p less than 0.001 for each). This study suggests that dipyridamole + handgrip stress imaging with PET can be used to assess changes in myocardial perfusion reserve before and after PTCA with the potential for determining restenosis noninvasively.

Relation between geometric dimensions of coronary artery stenoses and myocardial perfusion reserve in man.

To determine the relation between stenosis anatomy and perfusion in man, 31 patients had quantitative coronary arteriography and positron imaging (PET) with Rb-82 or N-13 ammonia at rest and after dipyridamole-handgrip stress. 10 patients were also studied after angioplasty (total stenoses = 41). Percent narrowing and absolute cross-sectional luminal area were related through a quadratic function to myocardial perfusion reserve determined with PET. Arteriographically determined coronary flow reserve was linearly related to relative myocardial perfusion reserve as expected, based on the derivation of equations for stenosis flow reserve. All of the correlations had considerable scatter, indicating that no single measurement derived by coronary arteriography was a good indicator of perfusion reserve by PET in individual patients. This study provides the relation between all anatomic dimensions of coronary artery stenoses and myocardial perfusion reserve in man, and suggests that PET indicates the functional significance of coronary artery stenoses for clinical purposes.

The prognostic significance of lymph-vascular space invasion in stage I endometrial cancer.

Surgical specimens from 111 patients with Stage I endometrial cancer were reviewed for the presence of lymph-vascular space invasion by tumor cells. Lymph-vascular space invasion was noted in 16 cases, and occurred most frequently in poorly differentiated tumors with deep myometrial penetration. Tumor recurrence developed in 44% of patients whose tumors demonstrated lymph-vascular space invasion as opposed to only 2% of patients without this finding (p less than 0.001). Of seven patients with lymph-vascular space invasion who experienced tumor recurrence, five developed extra-pelvic metastases. Discriminant function analysis of these data revealed a statistically significant correlation between lymph-vascular space invasion and tumor recurrence, independent of histologic differentiation of myometrial penetration. These findings suggest that lymph-vascular space invasion by tumor cells is an important prognostic variable in Stage I endometrial cancer which should be considered in treatment planning.

Light and electron microscopic study on the pineal complex of the coelacanth, Latimeria chalumnae Smith.

The pineal complex of the coelacanth, Latimeria chalumnae was studied light and electron microscopically. It consists of two vesicles representing parapineal and pineal organs. Both occur intracranially and openly communicate with each other and the brain ventricle. The entire complex shows a striking photoreceptor morphology with sensory, ependymal and nerve cells. The last cell type is more abundant in the parapineal vesicle than in the pineal organ. The following ultrastructural details of the parapineal are noteworthy: 1. The sensory cells possess large inner and outer segments protruding freely in the vesicular cavity. The outer segments measure 8-10 mum in length and consist of as many as 275 lamellae. The basal processes of these cells terminate in neuropil-like regions. Occasionally, dense granules (500-1000 A) of uncertain identity occur in the perinuclear and inner segment cytoplasm of the cells. 2. The supporting cells are of the ependymal type. Their cytoplasm contains a filamentous feltwork and pinocytotic vesicles, but lacks secretory granules. Cytosomes are particularly abundant in cell processes in the neuropil-like zones. The basal end-feet of these cells isolate the receptor and nerve cells from the perivascular space. 3. In the neuropil-like regions, terminals of sensory cells make synaptic contacts with neuronal dendrites. Synaptic ribbon-like profiles in the terminals characterize the contact zones. Only unmyelinated nerve fibers could be observed in the small area of the tissue examined. The results are discussed with regard to photoreceptive and secretory functions of the pineal complex and its evolution in lower vertebrates.