Comparison of normal piglet bladder damage after PDT with oral or intravesical administration of ALA.

5-Aminolaevulinic-acid (ALA) can be used as an alternative drug in photodynamic therapy of the bladder, since the selective formation of protoporphyrin IX (PpIX) in the tumour and the virtual absence of induced skin photosensitivity are theoretically advantageous for clinical use. A preclinical study was performed, using an in vivo normal piglet bladder model, in order to determine the maximum drug and light doses for reversible tissue damage. Various ALA doses were administered either orally or instilled in the bladder and different radiant exposures were applied. Bladder biopsies were taken at regular intervals and tissue damage was investigated histologically. After oral ALA-administration the PpIX concentration was determined in plasma, erythrocytes and various tissues. In the case of oral administration, reversible bladder damage was observed using 60-75 mg/kg ALA combined with a radiant exposure of 100 J/cm(2) (direct radiant exposure plus scattered 632 nm light) 5-7 h later. For an oral ALA dose of up to 150 mg/kg, the maximum PpIX concentration is reached at approximately 5 h following administration and in neither skin nor bladder tissue is PpIX present at 10-11 h after administration. This ALA dose combined with a radiant exposure of 200 J/cm(2) produces irreversible bladder damage (extensive necrosis and ulceration). In the case of intravesical instillation for 4-4.75 h, an ALA dose of 2.5 g in 50 ml phosphate buffered saline and a radiant exposure of 100 J/cm(2) are still too high to obtain reversible tissue damage; at this dose one of the 13 pigs developed a shrunken bladder with a fibrotic, thickened bladder wall. These drug and light combinations reported above should be regarded as upper limits in pigs and can serve as an indication for the toxicity of the treatment in a clinical setting.

Hemodynamic changes with right lateral decubitus body positioning in the tilted porcine heart.

BACKGROUND: In beating-heart coronary surgical procedures, exposure of posterior vessels through sternotomy causes cardiac function to deteriorate. We hypothesized that turning the subject to the right lateral decubitus position before cardiac retraction improves exposure of posterior vessels and preserves cardiac pump function on displacement. METHODS: Eight 80-kg open-chest pigs were instrumented with catheter-tip manometers. After a stepwise 60-degree turn to the right lateral decubitus position of the body, the heart was retracted anteriorly to 90 degrees with a suction stabilizer. RESULTS: Right lateral body positioning caused an approximately 45-degree right deviation of the apex, thereby exposing the left atrial groove. Stroke volume, mean arterial pressure, right atrial pressure, and right ventricular end-diastolic pressure increased to 106% +/- 5% (mean +/- standard error of the mean, p = 0.31), 106% +/- 3% (p = 0.01), 129% +/- 8% (p = 0.001), and 171% +/- 14% (p = 0.002), respectively, compared with control values. In contrast, left atrial pressure decreased to 73% +/- 6% (p = 0.007), whereas left ventricular preload remained unchanged (110% +/- 8%, p = 0.26). Additional anterior displacement to 90 degrees fully exposed the posterior vessels, and stroke volume decreased to 90% +/- 3% (p = 0.01) and mean arterial pressure to 93% +/- 5% (p = 0.07) at the expense of further increased right ventricular preload (256% +/- 28%, p < 0.001). CONCLUSIONS: By placing the subject in the right lateral decubitus position, exposure through sternotomy of posterior vessels in the beating porcine heart was facilitated while mean arterial pressure was maintained.

Exposure of circumflex branches in the tilted, beating porcine heart: echocardiographic evidence of right ventricular deformation and the effect of right or left heart bypass.

OBJECTIVE: In off-pump coronary surgery, exposure of posterior vessels via sternotomy causes deterioration of cardiac function. Changes in ventricular geometry, valve competence, and hemodynamics after retraction of the beating heart were studied. Subsequently, the modifying effect of right or left heart bypass was investigated. METHODS: In six 80-kg pigs, an ultrasound probe was attached to the backside of the left ventricle and the heart was fully retracted with a suction tissue stabilizer. Five pigs underwent additional pump support. RESULTS: During retraction, the right ventricle was squeezed between the pericardium and interventricular septum, thereby decreasing its diastolic cross-sectional area by 62% +/- 6% (P <.001) while, concomitantly, right ventricular end-diastolic pressure increased to 165% +/- 19% (P =.004) of basal values. Stroke volume and mean arterial pressure decreased by 29% +/- 6% and 23% +/- 8% (P =.007 and P =.02, respectively). Left ventricular shape became somewhat elliptic without changes in preload pressure, and its diastolic cross-sectional area decreased by 20% +/- 3% (P =.001). All valves were competent. Right heart bypass restored left ventricular cross-sectional area, stroke volume, and mean arterial pressure. In contrast, left heart bypass increased blood pressure only marginally. CONCLUSIONS: Ninety-degree anterior displacement of the beating porcine heart caused primarily right ventricular dysfunction as a result of mechanical interference with diastolic expansion without concurring valvular incompetence. Right heart bypass normalized stroke volume and mean arterial pressure by increasing left ventricular preload; in contrast, left heart bypass failed to restore systemic circulation.

A novel one-shot anastomotic stapler prototype for coronary bypass grafting on the beating heart: feasibility in the pig.

OBJECTIVE: The nonpenetrating, arcuate-legged clip has proved its ability to provide a high-quality microvascular anastomosis. This study assessed the feasibility of constructing a coronary end-to-side anastomosis on the beating heart with a novel mechanical, sutureless anastomotic device that applies 12 circumferential clips simultaneously. METHODS: In 14 consecutive pigs (70-90 kg), the left internal thoracic artery (diameter, 3 mm) was grafted to the left anterior descending coronary artery (diameter, 3 mm) by means of a one-shot anastomotic stapler prototype. Endothelial denudation, medial necrosis, and intimal hyperplasia were analyzed quantitatively and compared with those seen in conventionally sutured anastomoses (n = 4). RESULTS: In 8 of 14 anastomoses, the one-shot anastomotic stapler successfully applied all 12 clips circumferentially across the everted arteriotomy edges. In the remaining, either 1 (n = 4) or 3 and 4 adjoining malaligned clips had to be replaced manually with a single-clip applicator. Coronary occlusion was limited to approximately 3 minutes. At follow-up, all anastomoses were patent angiographically. At 2 days, in 2 of 7 cases, a local coronary dissection was observed, and there was a considerable loss of endothelial cells and medial damage. At 28 days, however, minimal intimal hyperplasia was seen at the anastomotic lining, although more pronounced when compared with conventionally sutured anastomoses. CONCLUSIONS: The one-shot anastomotic stapler prototype enabled short-occlusive (3 minutes), sutureless end-to-side grafting on the beating porcine heart. In spite of early endothelial and medial damage and 2 local dissections, all anastomoses remained patent with minimal intimal hyperplasia at 4 weeks.

Temporary luminal arteriotomy seal: II. Coronary artery bypass grafting on the beating heart.

BACKGROUND: This study assessed the feasibility of applying a temporary luminal arteriotomy seal during end-to-side coronary artery bypass grafting on the beating heart. METHODS: In 18 consecutive pigs, the left internal mammary artery was grafted to the left anterior descending coronary artery, and the arteriotomy was temporarily sealed luminally by a 200-microm-thick polyurethane seal. Endothelial denudation, medial necrosis, and intimal hyperplasia were measured quantitatively and compared with conventionally sutured anastomoses (n=4 pigs). RESULTS: Insertion and retrieval of the seal required 28+/-12 and 11+/-6 seconds, respectively. Including the arteriotomy, coronary artery occlusion was limited to about 80 seconds. The seal provided a bloodless arteriotomy in all anastomoses with unimpeded coronary artery blood flow. Endothelial denudation was limited to two thirds of the circumference of the coronary artery. No medial necrosis was found. Intimal hyperplasia at the suture line was small, although more pronounced when compared with conventionally sutured anastomoses. CONCLUSIONS: In off-pump, beating-heart coronary artery bypass grafting, the temporary luminal arteriotomy seal provided a bloodless arteriotomy with negligible obstruction to coronary artery blood flow, and with a minimum of arterial wall damage. It is conceivable that this seal may expand the indications for coronary surgical procedures without cardiopulmonary bypass.

Vertical displacement of the beating heart by the octopus tissue stabilizer: influence on coronary flow.

BACKGROUND: In beating heart coronary artery bypass graft operations, biventricular pump failure, as observed after exposure of the posterior circumflex branches by sternotomy, may originate from mechanical obstruction to coronary flow. METHODS: Regional coronary blood flow was measured in 8 anesthetized, paced, beta-blocked pigs, and the beating heart was fully retracted. RESULTS: Displacement decreased cardiac output from 4.8 +/- 1.1 L/min (mean +/- standard deviation) to 2.8 +/- 1.2 L/min (p < 0.001), a 42% +/- 6% decrease that resulted in a decrease in mean arterial pressure by 48% +/- 6% (mean +/- standard error of the mean; p < 0.001) and a reduction in coronary blood flow in the left anterior descending coronary artery, the right coronary artery, and the circumflex coronary artery by 34% +/- 6%, 25% +/- 8%, and 50% +/- 10%, respectively (all p < 0.05 versus baseline). Relative circumflex coronary artery flow was 20.1% +/- 8.3% lower than the combined relative value of left anterior descending coronary artery and right coronary artery flows (p = 0.046). Subsequent 20 degrees head-down tilt significantly increased ventricular preload pressures and restored cardiac output and mean arterial pressure as well as coronary blood flow. CONCLUSIONS: It is inferred that coronary blood flow was not mechanically obstructed during anterior displacement of the porcine beating heart, because augmentation of preloads by the maneuver of Trendelenburg restored coronary flow parallel to the recovery of cardiac output and mean arterial pressure while the heart remained retracted by 90 degrees.

Temporary luminal arteriotomy seal for bypass grafting.

BACKGROUND: To enable off-pump coronary operations in a bloodless surgical field without ischemic complications, we developed and assessed a temporary luminal arteriotomy seal in a porcine carotid artery bypass graft model. METHODS: In 16 consecutive pigs (25 kg, 32 anastomoses) the arteriotomy was sealed luminally by a polyurethane elliptic convex seal. Endothelial denudation, medial necrosis, and intimal hyperplasia were measured quantitatively and compared with those seen in conventionally sutured anastomoses. RESULTS: The median occlusive time upon insertion or retrieval was 90 and 82 seconds, including the arteriotomy and securing the anastomosis, respectively. Once properly positioned, the seal provided a bloodless arteriotomy in all anastomoses. Microsurgical suturing was performed without leakage of the seal and with unimpeded flow. In the recipient artery, endothelial denudation was limited to one third of its circumference. No medial necrosis was found. Intimal hyperplasia at heel and toe was not significantly different from that seen in conventionally sutured anastomoses. CONCLUSIONS: During end-to-side bypass grafting, the temporary luminal arteriotomy seal provided a bloodless surgical field without interfering with recipient artery blood flow and with minimal damage to the arterial wall.

Ultrasonography in acute interstitial laser irradiation of the pig brain: preliminary results.

In this preliminary study, the use of real-time ultrasonography to visualize the effects of acute interstitial Nd:YAG laser irradiation was investigated in the normal pig brain. In six pigs, a craniotomy was performed. In the frontal or temporal lobe, a thermal laser lesion was made using a 600-micron-diameter optical fiber at powers of 1 W, 2 W, and 4 W with exposure times of 5 min and 10 min. Ten to thirty minutes after laser irradiation, the pigs were sacrificed. Ultrasound imaging was performed before, during, and after laser irradiation. During laser irradiation, a clear hyperechogenic area was observed around the fiber tip. The onset of the changes and the extent of the lesion were dependent on the power and exposure time. Histologic examination showed thermal lesions consisting of coagulation necrosis and edema. The size of the lesions correlated well with size on ultrasound imaging. The maximal lesion dimension was 12 mm in diameter (4 W for 5 min). In conclusion, within the limitations of this experimental setup, it is feasible to visualize interstitial laser-induced lesions in the brain by ultrasonography. This method is safe and simple and may be helpful in future applications of interstitial thermotherapy in brain tissue.

The effect of elevated arterial free fatty acid concentrations on hemodynamics and myocardial metabolism and blood flow during ischemia.

In the present investigation the effect of elevated arterial free fatty acid (FFA) concentrations on regional myocardial blood flow (MBF), myocardial metabolism and hemodynamics during ischemia was studied in anesthetized dogs. Ischemia was induced by stenosis of the left interventricular coronary artery. Mean poststenotic coronary artery pressure was kept constant during ischemia. FFA concentrations were elevated by intravenous injection of heparin (group I), intralipid (group II) or both substances (group III). After elevation of FFA concentrations by heparin alone or together with intralipid, heart rate gradually increased, while aortic pressure tended to decrease. Slight elevation of arterial FFA levels (up to 0.30 mM, group I, and up to 0.53 mM, group II) had no significant effect on total MBF and uptake of glucose, FFA, and oxygen or release of lactate in the ischemic myocardium. However, elevating arterial FFA levels up to 0.81 mM (Group III), significantly decreased total MBF (6%), endo/epicardial blood flow ratio (13%), and oxygen uptake (34%) in the ischemic myocardium and resulted in release of lactate from this area. The release of potassium, inorganic phosphate and H+ as well as plasma CO2 concentration were not influenced. Neither was the uptake of glucose and FFA. These findings suggest that elevated arterial FFA concentrations can decrease MBF and augment lactate production in the ischemic myocardium.

In vivo cinematographic analysis of behavior of the aortic valve.

In open-chest dogs direct-cinematographic high-speed recordings of aortic valve movement were made using a thin flexible fiberscope. Simultaneously ECG, ascending aortic flow (electromagnetically), and the pressures in the aorta, left ventricle, and left atrium were recorded. Replacement of blood by a transparent liquid (Tyrode solution) was done with two roller pumps, one connected to the left atrium and the other to the femoral artery. Free outflow occurred through a cannula in the pulmonary artery. Comparison of the film frames with the aortic flow signals revealed that 1) the valve was completely open at the moment that aortic flow had reached about 75% of its maximum value; 2) the opening time was 32 ms; 3) valve closure started before the onset of aortic flow deceleration; 4) at least 80% of the closure was completed before aortic flow becomes zero; 5) complete valve closing coincided with the moment of maximum backflow in the valve; 6) the shape of the valvular orifice at complete opening was almost circular; and 7) fluid viscosity had no significant effect on valve closure.