Holmium-YAG and carbon dioxide laser ablation of normal and infarcted myocardium in the canine model

Surgical and transcatheter ablative treatment of ventricular tachycardias is based on endocardial mapping and removal of myocardial areas involved in sustaining the arrhythmia. Recently, argon and neodymium-YAG laser energy have been employed for the ablative treatment of ventricular tachycardia. In the present study the effects of holmium-YAG laser irradiation on normal and infarcted myocardium in the canine model were compared with those of the CO₂ laser. Myocardial infarction was created in 11 dogs by a two-stage left anterior descending coronary artery ligation. Laser irradiation of normal and infarcted myocardium was performed at about 1, 4 and 12 weeks following ligation, with energies of 5, 10, 20 and 30 J. A total of 218 irradiation induced craters were sectioned through the central axis and the evaporized, vacuole and denatured crater areas were morphometrically calculated. Total crater areas following holmium-YAG laser irradiation were significantly larger, with shallower penetration but larger lateral extension of evaporized, vacuole and denaturation areas. Perforations occurred only with CO₂ laser irradiation. Effects on normal and infarcted myocardium were similar and independent of infarct age. It is concluded that the holmium-YAG laser is probably more effective and safer than the CO₂ laser for myocardial ablation.     

The pregnant spontaneously hypertensive rat as a model of asymmetric intrauterine growth retardation and neurodevelopmental delay.

INTRODUCTION: Hypertension in pregnancy and vascular placental insufficiency are considered common pathogenic factors in human intrauterine growth retardation (IUGR). IUGR neonates experience higher mortality, and the surviving infants have a higher incidence of neurological and intellectual impairment. METHODS: To mimic this condition, we used pregnant spontaneously hypertensive rats (SHR) and performed biometric measurements on Embryonic Day 20, postnatal developmental reflexes, and locomotor activity evaluations. RESULTS: SHR fetuses had significant decreased body weight compared to the Wistar-Kyoto control fetuses (1.51+/-0.02 g vs. 2.05+/-0.01 g, respectively; p<0.0001), and were relatively microcephalic (2.86+/-0.04 cm vs. 3.3+/-0.03 cm, respectively; p<0.0001). Their cephalization index (head circumference/body weight) was increased (1.88+/-0.03 vs. 1.62+/-0.02, respectively; p<0.0001), indicating a "brain-sparing" process. The disproportional ratio indicated that the IUGR type in this model is asymmetric. The SHR pups exhibited a significant (p<0.04) neurodevelopmental delay in the acquisition of neonatal reflexes (righting, negative geotaxis, placing), but they spontaneously caught up with the control pups after approximately 10 days. On Day 30, the SHR pups exhibited significantly increased walking speed and distance and spent less time in quadrant than the controls (p<0.002). CONCLUSION: We speculate that the model of pregnant SHR closely simulate human IUGR caused by hypertension in pregnancy and should enable investigation of mechanisms of hypertension-mediated placenta-vascular injury as well as provide a system for preclinical evaluations of future preventive neuroprotective treatments.     

Captopril, but not diltiazem, favorably affects the course of early chronic renal disease in rats

The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases.     

Thyroid Dysfunction in Patients Treated With Sunitinib or Sorafenib

IntroductionSunitinib and sorafenib are tyrosine kinase inhibitors used in metastatic renal cell carcinoma and are known to cause hypothyroidism in a subset of patients. The goal of this study was to better characterize the development of hypothyroidism in patients and to examine its relationship to progression-free survival.Patients and MethodsA retrospective chart review was performed on patients treated with sunitinib or sorafenib from January 1, 2005, to January 1, 2011. Data pertaining to the treatment course and development of hypothyroidism were extracted. Patients with hypothyroidism at the beginning of treatment were analyzed separately.ResultsA total of 73 treatment periods had sufficient data to analyze. Among patients with normal baseline thyroid function, 15 (44%) of 34 patients treated with sunitinib and 6 (27%) of 22 patients treated with sorafenib developed hypothyroidism. The hazard ratio for the development of hypothyroidism with sorafenib vs. sunitinib treatment was significant, at 0.38 (95% CI, 0.14-0.97). There was a statistically significant difference in the progression-free survival between patients who developed hypothyroidism while receiving treatment compared with those who did not, 18.2 vs. 10.1 months (P = .01).ConclusionsThis study demonstrated a significant difference in the incidence of hypothyroidism during treatment with sunitinib and sorafenib, with a higher incidence of hypothyroidism in patients treated with sunitinib. The development of hypothyroidism was associated with a longer progression-free survival.     

Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats

Nonsteroidal anti-inflammatory drugs display a chemopreventive effect on polyps and cancer of the large bowel. This study evaluated the inhibitory effect of aspirin on the distribution and growth of aberrant crypt foci (ACF), the earliest putative preneoplastic and early neoplastic lesions in a rat model. For initiation of ACF, Sprague Dawley rats were injected with azoxymethane (30 mg/kg), a well-established rat carcinogen. After the second injection the rats were allocated to three groups, which received 0.2% or 0.6% aspirin or the solvent only (control group). After 6 weeks the animals were killed, and their colons removed, fixed in formalin, and screened for distribution and size of ACF, separately for middle and distal parts of the large intestine. The rats injected with azoxymethane showed a 100% incidence of ACF. Administration of 0.2% and 0.6% aspirin resulted in 55% and 54% reduction, respectively, in overall frequency of ACF. Aspirin significantly reduced the frequency of medium-sized (four to six crypts per focus) and large (three to six crypts per focus) but not the small (one to three crypts per focus) ACF. In the control group the ACF of the same multiplicity were larger than those in the aspirin-treated rats. No statistically significant difference in ACF-inhibiting effect was noted between 0.6% and 0.2% aspirin solution. Aspirin given at a concentration of either 0.2% of 0.6% thus has a chemopreventive effect on ACF, acting on postinitiation stage of azoxymethane-induced colonic carcinogenesis model in rats. Accepted: 20 July 1998