Cardiovascular Research 1992;26:22 1-225
22 1
Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig Albert0 J Crottogini, Peter Willshaw, Juan G Barra, Elena C Lascano, and Ricardo H Pichel
T
he left anterior descending coronary artery supplies not only the left ventricular anterior wall and anterior septum, but also the paraseptal part of the right ventricular anterior wall. This feature is similar in humans and pigs. The effect of acute occlusion of the left anterior descending artery on left ventricular anterior wall motion has been extensively studied in anae~thetisedl-'~and x I&IX conscious animals. These studies reveal that approximately 30 seconds after acute occlusion of the proximal left anterior descending artery, the left ventricular anterior wall starts to diselay systolic bulging, as evidenced by paradoxical thinning' - 'w' I* and lengthening3 l 3 " during systole. However, little is known about the concomitant motion changes undergone by the right ventricular anterior wall supplied by this artery. This information is of clinical interest since acute occlusion of the proximal left anterior descending artery compromises both its left ventricular and its right ventricular beds and would therefore be expected to induce motion changes in the anterior walls of both ventricles. The objective of the present study was thus to examine regional wall thickening of the right and left ventricular anterior walls supplied by the left anterior descending artery during transitory proximal occlusion in conscious, unsedated pigs.
We also analysed regional wall thickness changes in remote non-ischaemic zones of the right and left ventricular walls. Methods Surgical preparation Eight Landrace pigs of either sex and weighing 22.6(SD 2.7) kg (range: 19 to 28 kg) were used in this study. The experiments were performed in accordance with the Guiding Principles of the American Physiological Society concerning the use of experimental animals. The pigs were premedicated with intramuscular phenothiazine maleate (1 mg.kg-l) and anaesthetised using intravenous thiopentone sodium (20 mg.kg-l) for induction and 0.8% enflurane for maintenance, carried in a stream of pure oxygen via a Bain tube. Mechanical ventilation was provided by a Mark VIII ventilator (Bird Corporation, Palm Springs, CA, USA). A sterile thoracotomy was performed at the fourth left intercostal space. The heart was suspended in a pericardial cradle and four pairs of piezoelectric microcrystals (5 MHz) were positioned to measure right and left ventricular anterior and lateral wall thicknesses, following the procedure described by Sasayama et al. l9In all four pairs, the endocardia1 crystal was 2 mm in diameter and the epicardial crystal 5 mm in diameter. In order to avoid
Research and Teaching Department, Favaloro Foundation, Solis 453, 1078 Buenos Aires, Argentina: A J Crottogini, P Willshaw, J G Barra, E C Lascano, R H Pichel. Correspondence to Dr Crottogini
Downloaded from by guest on March 21, 2016
Objective: In humans, the left anterior descending coronary artery supplies the left ventricular wall, anterior septum and the paraseptal part of the right ventricular anterior wall. Our aim was to study the effects of acute left anterior descending coronary occlusion on wall thickening in the regions of the left and right ventricular anterior walls supplied by the artery, and in remote, non-ischaemic regions of both ventricles. Methods: Systolic wall thickening (defined as percent thickening with respect to end diastolic wall thickness) was studied in eight conscious pigs every 15 s during 1 min of acute left anterior descending coronary occlusion by a cuff occluder, and every 30 s during 4 min of reperfusion. Pigs were instrumented with ultrasonic microcrystals measuring wall thickness in the anterior walls (left anterior descending artery territory) and lateral walls (left circumflex or right coronary artery territory) of both ventricles, and a left ventricular pressure microtransducer. Results: During control and reperfusion, both anterior walls displayed similar systolic thickening. During coronary occlusion, the left ventricular anterior wall showed paradoxical systolic thinning (dyskinesia) whereas the right ventricular anterior wall showed only hypokinesia. Conclusions: In the presence of equal blood flow deprivation, the right ventricular anterior wall supplied by the left anterior descending coronary artery displays a significantly lesser degree of functional impairment than the left ventricular anterior wall supplied by the same artery. This differential effect may be due to mechanical unloading of the right ventricular anterior wall resulting from left ventricular anterior wall ischaemia. This afterload reduction due to decreased mechanical interaction between the two walls would allow the right ventricular anterior wall to express its contractile reserve in the form of systolic thickening.
222
Crottogini, Willshuw, Burru, Luscuno, Pichel
underestimation of the thickness of the naturally thin wall of the right ventricle, the endocardial crystals of this wall were not provided with an epoxy lens, this being replaced by a thin planar coating of epoxy resin. Using the distribution of the epicardial vessels as a guide. we positioned both anterior wall crystals well within the left anterior descending coronary artery bed, and both lateral wall crystals in zones remote from the territories to be rendered ischaemic. Using topical application of papaverine to avoid arterial spasm, the left anterior descending artery was dissected free at its origin and a cuff occluder positioned proximal to all side branches supplying the right ventricular wall. A high fidelity pressure microtransducer (Konigsberg P7) together with a fluid filled catheter for its calibration was inserted in the left ventricular cavity through the apex. A fluid filled catheter was inserted into the left atrium as part of a separate protocol (see below) and finally another fluid filled catheter was inserted into the right ventricle for measurement of pressure and for administration of a lethal injection at the end of the experiment. All catheters and cables were tunnelled under the skin to emerge at the interscapular space. The thoracotomy was closed without repair of the pericardium. The fluid filled catheters were flushed daily using heparinised saline. All pigs were treated daily with ampicillin (30 rngkg-') starting on the second postoperative day.
Datu rinulysis Left and right ventricular pressures and the four wall thickness signals were digitised every 5 ms (Data Translation 2801-A 12 bit A/D board, Marlborough, MA, USA) under control of a personal computer. End diastole was defined to occur at the onset of the rapid upstroke of the digitally derived left ventricular dP/dt signal, and end systole was defined as the moment of maximum wall thickness during a period of 20 ms preceeding the peak negative value of the digitally derived left ventricular dP/dt." In each experimental step, values for haemodynamic and dimension variables were obtained by averaging 13(SD 2 ) (range: 9 to 20) consecutive beats. Calculated haemodynamic variables were heart rate, right ventricular end diastolic pressure, right ventricular end systolic pressure, left ventricular end diastolic pressure, left ventricular peak systolic pressure, and maximum left ventricular dP/dt (dP/ dtmx). Measured dimension variables were end systolic thickness (EST) and end diastolic thickness (EDT) for left and right ventricular anterior wall and lateral wall. Dimension data were expressed in mm and as percent systolic wall thickening (%Th) according to the equation:
%Th = 100 X (EST-EDT)/EDT Stutisticul unu1ysi.r Values are expressed as mean (SD). For each experimental step, right ventricular dimension data were compared to left ventricular dimension data using a paired difference t test. Haemodynamic data were processed using analysis of variance. When the F ratio yielded significant differences, the values at 60 s of ischaemia and at I , 2, and 4 min of reperfusion were compared against the control values using the Bonferroni correction. A p value
22 1
Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig Albert0 J Crottogini, Peter Willshaw, Juan G Barra, Elena C Lascano, and Ricardo H Pichel
T
he left anterior descending coronary artery supplies not only the left ventricular anterior wall and anterior septum, but also the paraseptal part of the right ventricular anterior wall. This feature is similar in humans and pigs. The effect of acute occlusion of the left anterior descending artery on left ventricular anterior wall motion has been extensively studied in anae~thetisedl-'~and x I&IX conscious animals. These studies reveal that approximately 30 seconds after acute occlusion of the proximal left anterior descending artery, the left ventricular anterior wall starts to diselay systolic bulging, as evidenced by paradoxical thinning' - 'w' I* and lengthening3 l 3 " during systole. However, little is known about the concomitant motion changes undergone by the right ventricular anterior wall supplied by this artery. This information is of clinical interest since acute occlusion of the proximal left anterior descending artery compromises both its left ventricular and its right ventricular beds and would therefore be expected to induce motion changes in the anterior walls of both ventricles. The objective of the present study was thus to examine regional wall thickening of the right and left ventricular anterior walls supplied by the left anterior descending artery during transitory proximal occlusion in conscious, unsedated pigs.
We also analysed regional wall thickness changes in remote non-ischaemic zones of the right and left ventricular walls. Methods Surgical preparation Eight Landrace pigs of either sex and weighing 22.6(SD 2.7) kg (range: 19 to 28 kg) were used in this study. The experiments were performed in accordance with the Guiding Principles of the American Physiological Society concerning the use of experimental animals. The pigs were premedicated with intramuscular phenothiazine maleate (1 mg.kg-l) and anaesthetised using intravenous thiopentone sodium (20 mg.kg-l) for induction and 0.8% enflurane for maintenance, carried in a stream of pure oxygen via a Bain tube. Mechanical ventilation was provided by a Mark VIII ventilator (Bird Corporation, Palm Springs, CA, USA). A sterile thoracotomy was performed at the fourth left intercostal space. The heart was suspended in a pericardial cradle and four pairs of piezoelectric microcrystals (5 MHz) were positioned to measure right and left ventricular anterior and lateral wall thicknesses, following the procedure described by Sasayama et al. l9In all four pairs, the endocardia1 crystal was 2 mm in diameter and the epicardial crystal 5 mm in diameter. In order to avoid
Research and Teaching Department, Favaloro Foundation, Solis 453, 1078 Buenos Aires, Argentina: A J Crottogini, P Willshaw, J G Barra, E C Lascano, R H Pichel. Correspondence to Dr Crottogini
Downloaded from by guest on March 21, 2016
Objective: In humans, the left anterior descending coronary artery supplies the left ventricular wall, anterior septum and the paraseptal part of the right ventricular anterior wall. Our aim was to study the effects of acute left anterior descending coronary occlusion on wall thickening in the regions of the left and right ventricular anterior walls supplied by the artery, and in remote, non-ischaemic regions of both ventricles. Methods: Systolic wall thickening (defined as percent thickening with respect to end diastolic wall thickness) was studied in eight conscious pigs every 15 s during 1 min of acute left anterior descending coronary occlusion by a cuff occluder, and every 30 s during 4 min of reperfusion. Pigs were instrumented with ultrasonic microcrystals measuring wall thickness in the anterior walls (left anterior descending artery territory) and lateral walls (left circumflex or right coronary artery territory) of both ventricles, and a left ventricular pressure microtransducer. Results: During control and reperfusion, both anterior walls displayed similar systolic thickening. During coronary occlusion, the left ventricular anterior wall showed paradoxical systolic thinning (dyskinesia) whereas the right ventricular anterior wall showed only hypokinesia. Conclusions: In the presence of equal blood flow deprivation, the right ventricular anterior wall supplied by the left anterior descending coronary artery displays a significantly lesser degree of functional impairment than the left ventricular anterior wall supplied by the same artery. This differential effect may be due to mechanical unloading of the right ventricular anterior wall resulting from left ventricular anterior wall ischaemia. This afterload reduction due to decreased mechanical interaction between the two walls would allow the right ventricular anterior wall to express its contractile reserve in the form of systolic thickening.
222
Crottogini, Willshuw, Burru, Luscuno, Pichel
underestimation of the thickness of the naturally thin wall of the right ventricle, the endocardial crystals of this wall were not provided with an epoxy lens, this being replaced by a thin planar coating of epoxy resin. Using the distribution of the epicardial vessels as a guide. we positioned both anterior wall crystals well within the left anterior descending coronary artery bed, and both lateral wall crystals in zones remote from the territories to be rendered ischaemic. Using topical application of papaverine to avoid arterial spasm, the left anterior descending artery was dissected free at its origin and a cuff occluder positioned proximal to all side branches supplying the right ventricular wall. A high fidelity pressure microtransducer (Konigsberg P7) together with a fluid filled catheter for its calibration was inserted in the left ventricular cavity through the apex. A fluid filled catheter was inserted into the left atrium as part of a separate protocol (see below) and finally another fluid filled catheter was inserted into the right ventricle for measurement of pressure and for administration of a lethal injection at the end of the experiment. All catheters and cables were tunnelled under the skin to emerge at the interscapular space. The thoracotomy was closed without repair of the pericardium. The fluid filled catheters were flushed daily using heparinised saline. All pigs were treated daily with ampicillin (30 rngkg-') starting on the second postoperative day.
Datu rinulysis Left and right ventricular pressures and the four wall thickness signals were digitised every 5 ms (Data Translation 2801-A 12 bit A/D board, Marlborough, MA, USA) under control of a personal computer. End diastole was defined to occur at the onset of the rapid upstroke of the digitally derived left ventricular dP/dt signal, and end systole was defined as the moment of maximum wall thickness during a period of 20 ms preceeding the peak negative value of the digitally derived left ventricular dP/dt." In each experimental step, values for haemodynamic and dimension variables were obtained by averaging 13(SD 2 ) (range: 9 to 20) consecutive beats. Calculated haemodynamic variables were heart rate, right ventricular end diastolic pressure, right ventricular end systolic pressure, left ventricular end diastolic pressure, left ventricular peak systolic pressure, and maximum left ventricular dP/dt (dP/ dtmx). Measured dimension variables were end systolic thickness (EST) and end diastolic thickness (EDT) for left and right ventricular anterior wall and lateral wall. Dimension data were expressed in mm and as percent systolic wall thickening (%Th) according to the equation:
%Th = 100 X (EST-EDT)/EDT Stutisticul unu1ysi.r Values are expressed as mean (SD). For each experimental step, right ventricular dimension data were compared to left ventricular dimension data using a paired difference t test. Haemodynamic data were processed using analysis of variance. When the F ratio yielded significant differences, the values at 60 s of ischaemia and at I , 2, and 4 min of reperfusion were compared against the control values using the Bonferroni correction. A p value
