Total Occlusion Time Research Articles

Magnetic Resonance Imaging of Acute Myocardial Infarction in Pigs Using Gd-Dtpa

Six pigs with coronary artery occlusion were investigated with MR imaging before and subsequently for about 2.5 hours at repeated intervals after the intravenous administration of Gd-DTPA (0.4 mmol/kg). The animals were sacrificed after a total occlusion time of 6 hours and the hearts were excised. The excised hearts were then reexamined in the MR equipment and stained with TTC (triphenyl tetrazolium) in order to define areas of infarction. Four control hearts with 6-hour-old infarctions were only imaged ex vivo without any previous administration of contrast media. In vivo, there was no clear demarcation of infarction with or without Gd-DTPA. Ex vivo, without any contrast media, the infarctions were poorly discriminated with a discretely increased signal intensity relative to normal myocardium in the T2 weighted images. Gd-DTPA was found to accumulate in the infarctions, which caused an elevated signal intensity most pronounced in the T1 weighted images. This considerably improved the delineation of the infarcted area.

Regional Variations of Laser Doppler Blood Flow in Ischemic Skin Flaps

An island skin flap was designed on the left inferior epigastric neurovascular bundle of anesthetized male rats. Blood flow was measured in situ with a laser Doppler flowmeter at 20 discrete points on a grid system (5 points in each quadrant of the flap) before and after surgery, or before vascular occlusion, during reperfusion, and 48 to 72 hours later. Two series of experiments were performed. In the first series, the raised flap was placed in a bath containing heated Ringer's solution and the left pedicle was cross-clamped. After 30 minutes, adenosine at a concentration that produced supramaximal vasodilatation, or its vehicle, was added to the bath. After 1 hour total occlusion time, the vascular clamp was released and adenosine treatment was continued for the first 30 minutes of reperfusion. In the second series, the protocol was similar except that adenosine, or its vehicle, was infused into the ischemic flap by means of the distal stump of the right inferior epigastric artery. After 48 to 72 hours, fluorescein was injected IV. The data showed a significant regional variation in baseline laser Doppler blood flow that was further altered by surgically raising the flap. Whereas proximal axial laser Doppler blood flow was essentially unchanged from the preoperative baseline, distal axial laser Doppler blood flow decreased 10 to 50 percent, and proximal and distal dependent laser Doppler blood flow decreased 50 to 80 percent. Thus no single value accurately reflected total flap perfusion. Necrosis occurred only in the dependent flap regions, which confirmed previous work. In the dependent regions, especially along the incision line, postoperative laser Doppler blood flow was lowest.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Collateral Regression in Conscious Dogs

To study the effect of long-term coronary reperfusion on regression of newly developed collateral vessels, the authors reoccluded the coronary artery for ten minutes following one to fifteen weeks of reperfusion. They repeated one- or two-minute occlusions of the left circumflex coronary artery (LCCA) in 8 conscious dogs. After 401 +/- 202 (SD) minutes of total LCCA occlusion time (35 +/- 19 days), The LCCA occlusion produced no sustained reduction in regional myocardial shortening and negligible reactive hyperemia. Upon reocclusion following a long-term reperfusion, the subendocardial segment shortening in the region at risk deteriorated markedly. At two minutes of occlusion, percent systolic shortening showed minimal values and thereafter gradually returned to the preocclusion resting levels within six to eight minutes of occlusion. In the presence of a resting heart rate similar to that at the time of functional recovery during the LCCA occlusion, long-term reperfusion did not modify the time course of regional functional response to the prolonged coronary occlusion. It is concluded that the newly developed collateral vessels still serve as significant blood-conveying conduits following a considerable period of reperfusion, and it requires approximately six to eight minutes to restore regional myocardial function in the collateral dependent zone following coronary reocclusion.

Importance of myocardial ischemia for coronary collateral development in conscious dogs

The purpose of this study was to evaluate the effects of myocardial ischemia on the development of collateral circulation. Thirteen conscious dogs were instrumented for serial measurements of subendocardial segment length in the area perfused by the left circumflex coronary artery, left circumflex coronary artery flow and left ventricular pressure. In 6 dogs (group A), 1 min left circumflex coronary artery occlusions were carried out at 30 min intervals. When the 442nd 1 min left circumflex coronary artery occlusion produced a reduction in segment shortening and a significant reactive hyperemia, the occlusion time was increased to 2 min. In the remaining 7 dogs (group B), 2 min left circumflex coronary artery occlusions were conducted hourly. In group A, following 451 ± 201 (SD) min of total occlusion time with the mixture of 1 and 2 min left circumflex coronary artery occlusions (43 ± 18 days) a left circumflex coronary artery occlusion produced no reduction in segment shortening and negligible reactive hyperemia. By contrast, in group B, 218 ± 99 min of total occlusion time (18 ± 8 days) was required to develop adequate collateral circulation. The relative contribution of the first and second 1 min of left circumflex coronary artery occlusion to the collateral development was mathematically evaluated. This analysis indicated that the second 1 min of left circumflex coronary artery occlusion is 4.43-fold more effective than the first 1 min of occlusion in terms of the collateral induction. We concluded that severe myocardial ischemia plays an important role in the development of collateral circulation.

Magnetic Resonance Imaging of Acute Myocardial Infarction in Pigs Using Gd-DTPA

Six pigs with coronary artery occlusion were investigated with MR imaging before and subsequently for about 2.5 hours at repeated intervals after the intravenous administration of Gd-DTPA (0.4 mmol/kg). The animals were sacrificed after a total occlusion time of 6 hours and the hearts were excised. The excised hearts were then reexamined in the MR equipment and stained with TTC (triphenyl tetrazolium) in order to define areas of infarction. Four control hearts with 6-hour-old infarctions were only imaged ex vivo without any previous administration of contrast media. In vivo, there was no clear demarcation of infarction with or without Gd-DTPA. Ex vivo, without any contrast media, the infarctions were poorly discriminated with a discretely increased signal intensity relative to normal myocardium in the T2 weighted images. Gd-DTPA was found to accumulate in the infarctions, which caused an elevated signal intensity most pronounced in the T1 weighted images. This considerably improved the delineation of the infarcted area.

Myocardial release of hypoxanthine and lactate during percutaneous transluminal coronary angioplasty

The response of myocardial lactate and hypoxanthine metabolism during percutaneous transluminal coronary angioplasty was studied in a series of 15 patients undergoing this procedure. A minimum of 4 balloon inflations was performed per patient with an average duration per occlusion of 49 ± 11 seconds (mean ± standard deviation) for a total occlusion time of 192 ± 40 seconds. Thermodilution coronary venous blood flow measured in the great cardiac vein decreased from control values of 72 ± 4 ml/min (mean ± standard error of the mean) to 47 ± 10 ml/min with the fourth coronary occlusion (p < 0.005). Arteriovenous lactate and hypoxanthine showed peak differences during the reactive hyperemia after the first 2 occlusions which did not increase after subsequent occlusions. Within minutes after the procedure, lactate and hypoxanthine efflux was no longer seen, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent alteration in lactate or hypoxanthine metabolism after percutaneous transluminal coronary angioplasty with 4 coronary occlusions of 40 to 60 seconds' duration, with a total occlusion time of 192 ± 40 seconds.

Reductions in regional myocardial function at rest in conscious dogs with chronically reduced regional coronary artery pressure.

We have examined the temporal response of regional subendocardial function in conscious chronically instrumented dogs following implantation of a circumflex ameroid occluder. Collateralization was limited by ligation of epicardial anastamoses between the circumflex and adjacent coronary arteries at the time of instrumentation. Sonomicrometrically measured regional function in the circumflex coronary artery became depressed relative to that in the left anterior descending coronary artery bed under resting conditions with the onset of an aortic-circumflex pressure gradient of 15 +/- 2.9 mm Hg (mean +/- SEM). At the time of total ameroid occlusion, the ratio of circumflex to left anterior descending coronary artery function fell to 68 +/- 8% of control, with mean circumflex coronary pressure decreasing to 60 +/- 1.6 mm Hg. Following ameroid occlusion, distal coronary pressure increased, and circumflex function recovered towards control but remained depressed relative to that in the left anterior descending coronary artery for 2-4 weeks. Measurements of regional subendocardial perfusion suggested a dissociation between subendocardial flow and function prior to but not following coronary occlusion by the ameroid. We conclude that this model results in reductions in regional function that are relatively prolonged and are not readily attributable to subendocardial infarction or a critical reduction in resting coronary flow. The data suggest that functional adaptations in response to gradually developing coronary occlusion are more complex than those associated with acute reductions in coronary artery pressure and flow.

Protection against spinal cord ischemia with insulin-induced hypoglycemia

The effect of insulin-induced reduction in blood glucose to 65 +/- 20 mg/dl (mean +/- standard deviation) on recovery of electrophysiological function and extracellular lactate concentration was studied in a rabbit model of spinal cord ischemia. These results were compared to findings in animals with spinal cord ischemia that either were fasted overnight (fasted group: blood glucose 97 +/- 26 mg/dl) or had no pretreatment (control group: blood glucose 172 +/- 65 mg/dl). The aorta was occluded until the postsynaptic waves of the spinal somatosensory evoked potentials (SSEP's) had been absent for 20 minutes, a period of ischemia that produces paraplegia in 100% of untreated rabbits. The total aortic occlusion time was not significantly different in the three groups. Recovery of the SSEP's was significantly better in the insulin-treated animals than in the fasted or control animals. The N3 wave of the SSEP's, which has been found to correlate best with neurological recovery, returned to 65% +/- 48% of the preischemia amplitude in the insulin-treated animals, compared to 40% +/- 34% in the fasted group and 26% +/- 24% in the control animals. Extracellular lactate concentration in the spinal cord increased immediately after occlusion of the aorta, reached a plateau as the postsynaptic waves disappeared from the SSEP's, and then increased a second time during the first 15 minutes of reperfusion. The peak lactate concentration during ischemia and during reperfusion correlated with the preischemia glucose concentration (r = 0.60336 and r = 0.76930, respectively). Lactate concentration in the spinal cord was higher during ischemia and throughout the first 2 hours of reperfusion in the control and fasted animals than in the insulin-treated animals. During the 2nd hour of reperfusion, lactate concentration was significantly higher in the control animals than in the fasted animals. Reduction in blood glucose with insulin improves recovery of electrophysiological function after spinal cord ischemia, probably because of reduced lactic acid production, especially during the early reperfusion period.

One-Year Follow-Up after Thrombolytic Therapy in Acute Myocardial Infarction

Of a group of 92 consecutive patients who had suffered an acute myocardial infarct and whose symptoms lasted for less than 3 h, 86 underwent coronary recanalisation. Both mechanical and fibrinolytic methods were used. The combined administration of intravenous and intracoronary streptokinase led to the highest rate of reperfusion. In 67 patients (78%) myocardial reperfusion was achieved. Five patients (7·5%) underwent coronary bypass surgery during the hospital phase. They survived without a reinfarct. Of the other 62 patients, 12 suffered a non-fatal reinfarction and 4 patients expired. Coronary bypass surgery was performed on 13 patients, all of whom survived the operation without a reinfarct. After one year 91% of the successfully treated patients were alive, 19% had suffered a nonfatal reinfarct and 27% had undergone coronary surgery. Of the 19 unsuccessfully treated patients, 5 (26%) died, and 2 (11%) suffered a nonfatal reinfarct. The primary cause of death after recanalisation was a reinfarct with sudden cardiac death; in those unsuccessfully treated patients the primary cause was left heart failure and sudden cardiac death. Thallium scans after a 1-year period showed better results for posterior infarcts and a correlation between the size of the lesion and the total coronary occlusion time. No defects or incomplete defects were observed at a total occlusion time of less than 200 min. Thirty-three percent of those patients who underwent successful recanalisation of the LAD without a reinfarct showed no defects or only a partial defect. In those cases of successful recanalisation of RCA and LCX with no reinfarct within one year, 28% showed no defect or only partial defects. These patients who were treated with myocardial reperfusion following myocardial infarction appear to have a better prognosis than those treated by conventional means. After the hospital phase, reinfarct and death are rare occurrences. If indicated, acute coronary bypass surgery can be performed at a small risk.

Left ventricular function during transluminal angioplasty: a haemodynamic and angiographic study.

The response of left ventricular function, was studied in a series of patients undergoing percutaneous transluminal coronary angioplasty (PTCA). From 4 to 6 balloon inflations procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD), total occlusion time 252 +/- 140 sec. Analysis of left ventricular (LV) haemodynamics showed that the relaxation parameters peak negative rate of change in pressure and the early time constant of relaxation responded earliest to acute coronary occlusion while other parameters such as peak pressure, LV end-diastolic pressure, and peak positive rate of change of pressure responded more gradually and suggested a progressive depression in myocardial mechanics during the entire procedure. LV angiogram available in 14 patients indicate an early onset of asynchronous relaxation concurrent with the early response in peak -dP/dt and the time constant of early relaxation. All haemodynamic parameters fully recovered within minutes after the end of PTCA. The results of this study indicate no permanent dysfunction to global or regional myocardial mechanics, after PTCA with 4 to 6 coronary occlusions each lasting 40 to 60 seconds.

Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.

The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.

Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis.

We investigated the effects of brief intermittent periods of ischemia on myocardial viability. Brief periodic coronary occlusions were produced up to 18 times by inflating and deflating the balloon of an intracoronary No. 2F catheter for periods of 15, 10 or 5 minutes, followed by 15-minute periods of reperfusion. Creatine kinase (CK) release, triphenyl tetrazolium chloride staining, and light and electron microscopy were used to detect the presence of myocardial necrosis. For the study of CK release, blood was taken from the great cardiac vein and the aorta before and at 5-minute intervals during each left anterior descending coronary occlusion, as well as during and 1, 5, 10 and 15 minutes after balloon deflation. In seven of 24 dogs with 15-minute occlusions, in five of 21 dogs with 10-minute occlusions, and in three of 32 dogs with 5-minute occlusions, small but distinct areas of subendocardial necrosis were present. In all dogs with morphologic proof of necrosis, there was periodic release of CK into the great cardiac vein, which peaked immediately after reperfusion, reflecting CK washout. Thus, brief periods of ischemia, which when single do not cause necrosis, have a cumulative effect and may cause myocardial necrosis. This mechanism of necrosis may be relevant clinically in patients with frequent anginal episodes. Since many dogs of this study did not have any myocardial necrosis, the findings also suggest that intermittent reperfusion has a beneficial effect and may prevent necrosis, even when total occlusion time exceeds 200 minutes.

Time course of muscle metabolic changes during tourniquet ischemia in man.

Muscle biopsies form the vastus lateralis muscle of the thigh were obtained from 11 patients before and at 15-min intervals following tourniquet application and 15 min after tourniquet release. The total circulatory occlusion time varied from 60 to 120 min. The concentrations of lactate, creatine phosphate and adenosine triphosphate were determined, and the muscle temperature was recorded. During the ischemic period, the lactate concentration increased from 1.9 mmol x kg-1 wet wt to 14.9 mmol x kg-1 wet wt after 90 min of ischemia. During the last 30 min of ischemia, no further increase in lactate concentration was observed. The creatine phosphate concentration decreased from 20.4 to 5.2 mmol x kg-1 wt wt after 120 min of ischemia. The temperature fell rapidly during the first 15 min from 35.9 degrees to 33.5 degrees and was then constant until 95 min when a further small decrease was observed. The adenosine triphosphate concentration did not change significantly during the ischemic period.