Effect of a Mechanical vs a Pharmacologic Increase in Aortic Pressure on Coronary Blood Flow and Thrombolysis Induced by IV Administration of a Thrombolytic Agent (Materials and Methods)

In: Aortic Pressure

7 Jan 2014

Effect of a Mechanical vs a Pharmacologic Increase in Aortic Pressure on Coronary Blood Flow and Thrombolysis Induced by IV Administration of a Thrombolytic Agent (Materials and Methods)Eight dogs (24 to 34 kg) were anesthetized with IV pentobarbital sodium (30 mg/kg) that was supplemented as required to maintain anesthesia. Their treatment conformed to the guidelines of the University of Manitoba Animal Care Committee. Each dog was mechanically ventilated in a right lateral decubitus position via an endotracheal tube with 100% 02 with a tidal volume of 20 mL/kg. The respiratory rate was adjusted to maintain PaC02 between 25 and 45 mm Hg. Metabolic acidosis was treated with sodium bicarbonate to maintain arterial pH greater than 7.28. A catheter was inserted into the left carotid artery for measurement of BP and for the removal of 20 mL of blood for autologous clot formation. Blood, for gas analysis, was also removed via this catheter. IV lines were inserted into the right and left femoral and external jugular veins for infusion of norepinephrine, sodium bicarbonate, lidocaine, and for phlebotomy as required.

A thermistor-tipped flow-directed pulmonary artery catheter was inserted via the left external jugular vein and was positioned in the proximal pulmonary artery for measurement of thermodilution cardiac output (CO) and pulmonary artery diastolic pressure. The proximal port of the pulmonary artery catheter was used for injection of saline solution boluses for CO determination (Columbus Instruments; Columbus, Ohio). ECG, lead II, was used to monitor rate and rhythm. Lidocaine was given as required for ventricular premature depolarization. A Fogarty catheter was placed in the descending aorta via the right femoral artery. Effective placement of this catheter was confirmed by demonstrating that balloon inflation reproduc-ibly increased aortic pressure.

Following catheterization, all dogs received a 2-mL IV injection of pancuronium bromide (2 mg/mL). A 15-cm incision was made in the left fifth intercostal space to expose the heart. Positive end-expiratory pressure of 2 to 3 cm H20 was applied postthoracotomy. An incision was made in the pericardium to expose the left main coronary artery. The left anterior descending coronary artery was cleaned by blunt dissection and a calibrated 8-mm outer diameter flow probe (Carolina Instruments; King, NC) was placed distally. Subsequently, a piece of corticelli tape was threaded underneath the left anterior descending artery to steady it during cannulation with a 20-g 1.25-inch IV placement catheter (Ethalon IV; Criticon Canada Inc; Markham, Ontario). Following cannulation, the catheter was supported by two small strips of Teflon felt (Medox Medicals Inc; Oakglen, NY), one on either side of the catheter and secured to the pericardium. This catheter was used for injection of 0.3 g of radioactive clot. The flow probe was positioned as close to the tip of the catheter as possible. Measurement of left anterior descending artery blood flow before and after catheter placement demonstrated that the catheter did not affect the measured coronary blood flow. Figure 1 illustrates this preparation. Following intracoronary catheter placement, the dogs were allowed a 30-min stabilization period.

All catheters were connected to transducers (Statham P23 I.D.; Gould; Oxnard, Calif) that were leveled to the midstemum. The ECG was continuously recorded throughout the experiment. The output from all transducers and the flow probe was displayed on a 12-channel oscillograph (Electronics for Medicine; PPG Biomedical Systems; Lenexa, Kan) with recorder.

Radioactive Autologous Blood Clot Preparation

Each technetium-99m sulfur colloid preparation was prepared as previously described.

Protocol

After stabilization, baseline measurements (mean, systolic and diastolic BP, pulmonary artery diastolic pressure, heart rate, coronary artery blood flow, and CO were taken. Subsequently, 0.3 g of radioactive autologous clot was injected into the left anterior descending coronary artery via the catheter and was flushed through the catheter with normal saline solution. After a 20-min stabilization period, postclot measurements were obtained. Subsequently, all dogs were phlebotomized to decrease their systolic aortic pressure to approximately 75 mm Hg. In each dog, the rate of coronary thrombolysis was determined during a 15-min interval of rtPA infusion when the systolic aortic pressure had been increased to 130 mm Hg via Fogarty catheter inflation or by norepinephrine infusion. After ensuring steady-state conditions (stable systolic BP of approximately 130 mm Hg), 0.25 mg/kg of rtPA was infused IV over 15 min and the rate of thrombolysis was assessed. Subsequently, the Fogarty catheter was deflated or the norepinephrine infusion was stopped and systolic BP rapidly decreased to approximately 75 mm Hg. Then after 15 min, the alternate treatment was begun to increase the systolic BP to approximately 130 mm Hg. After approximately 10 min, the same dose of rtPA was infused over 15 min and the rate of thrombolysis again determined. Each dog was employed as its own control to eliminate intergroup variability. The initial use of norepinephrine or Fogarty catheter inflation was alternated from dog to dog to control for the effects of time. Employing this protocol in a previous study, we were able to reproducibly assess the effects of an intervention on coronary thrombolysis.

Assessment of Coronary Thrombolysis

Monitoring of cardiac radioactivity was achieved with a mobile gamma camera (Picker Dayna IV; Picker International Canada Inc; Winnipeg, Manitoba), equipped with a parallel hole collimator, coupled to a mobile computer (Medical Data Systems A2; Medtronic of Canada Ltd; Richmond, British Columbia). Dynamic images were acquired in a 64X 64-byte mode for 2.5 h at a rate of 60 s per frame. In each study, a region of interest was placed about the heart. To assess the rate of coronary thrombolysis, a percent radioactivity vs time plot was generated. A marker was placed at the onset of clot lysis. A second marker was placed on the plot at an interval 15 min after the onset of clot lysis. A regression line that best fit the data points within this interval was generated. The slope of the line defined the rate of clot lysis during this interval.

Statistical Analysis

Hemodynamic parameters were analyzed for a change with clot by paired t test. To assess the effect of increased systolic BP on coronary thrombolysis by norepinephrine infusion and Fogarty catheter inflation, the paired t test was employed. To assess the hemodynamic effects of norepinephrine infusion and catheter inflation, a two-way analysis of variance was performed. If a significant F value was obtained, Tukey’s test was applied to determine if there was a difference between mean values.


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