We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy prevents volume-overload hypertrophy in dogs with chronic mitral regurgitation (MR). Seven adult mongrel dogs receiving ramipril (R; 10 mg orally, twice/day) for 4 mo were compared with 11 dogs receiving no R (N) for 4 mo after induction of MR. Cine-magnetic resonance imaging demonstrated that left ventricular (LV) mass increased in the R-MR dogs [80 +/- 4 (SE) to 108 +/- 7 g, P < 0.01] and in the N-MR dogs (92 +/- 7 to 112 +/- 8 g, P < 0.001). LV myocyte cell length was greater in the R-MR and N-MR dogs (203 +/- 6 and 177 +/- 10 microns, respectively) than in normal (144 +/- 4 microns, P < 0.05) dogs. There was significant loss of the collagen weave pattern by scanning electron microscopy in both R-MR and N-MR dogs. LV ACE and chymase activities were significantly elevated in R-MR and N-MR compared with normal dogs. LV angiotensin II (ANG II) levels in the R-MR dogs (28 +/- 12 pg/g) were reduced to levels seen in normal dogs (28 +/- 4 pg/g) compared with N-MR dogs (72 +/- 11 pg/g, P < 0.05). Steady-state AT1-receptor mRNA levels decreased 66% in N-MR compared with normal dogs (P < 0.001) and increased 1.5-fold in R-MR compared with normal dogs (P < 0.01). Thus upregulation of the AT1 receptor in the R-MR hearts may provide a mechanism by which normal intracardiac ANG II levels could continue to mediate LV hypertrophy. However, the mechanism of dissolution collagen weave in both N-MR and R-MR hearts may be related to the stretch of volume overload.

Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 M, 0.1 ml/min, 60 min), and during ANG I ϩ the angiotensin-converting enzyme inhibitor captopril (

The current study was designed to test the hypothesis that intracardiac angiotensin-converting enzyme (ACE) activity, chymase-like activity, and angiotensin (ANG) peptide levels are increased and are positively related to wall stress estimates in response to the chronic low pressure volume overload of mitral regurgitation produced by percutaneous chordal rupture in the dog. Chronic mitral regurgitation (MR) resulted in an increase in left ventricular (LV) end-diastolic volume [59 +/- 11 (SD) to 103 +/- 32 ml, P < 0.001], LV mass (96 +/- 17 to 114 +/- 23 g, P < 0.001), and a decrease in the LV mass-to-end-diastolic volume ratio (1.64 +/- 0.22 to 1.16 +/- 0.23 g/ml, P < 0.001) measured by magnetic resonance imaging. In vitro studies of heart tissue extracts demonstrated that the majority of ANG II-forming activity was from chymase-like activity rather than from ACE activity in five normal (83.5 +/- 7.5 vs. 6.04 +/- 5.2%) and seven MR hearts (86 +/- 3.9 vs. 2.6 +/- 1.7%). ACE activity (1.22 +/- 0.22 vs. 3.55 +/- 0.62 mU/g, P < 0.05) and chymase-like activity (9.42 +/- 4.64 vs. 20.60 +/- 8.41 nmol.g-1.min-1, P < 0.05) were increased in MR compared with normal hearts. ACE activity correlated with the LV mass-to-volume ratio (r = -0.93, P < 0.001) and LV diastolic wall stress ( r = 0.71, P < 0.05); however, chymase-like activity did not correlate with any hemodynamic parameter. ANG II levels were significantly higher in the midwall of the left ventricle in MR hearts than in normal controls (85 +/- 39 vs. 27 +/- 16 pg/g, P < 0.01). Our results demonstrate a positive correlation between LV diastolic wall stress and increased ACE activity with increased ANG II stores, suggesting that mechanical wall stress activated intracardiac ACE. Although chymase accounted for most ANG II formation in vitro in extracts of both normal and MR dog hearts, the significance of this enzyme in vivo remains unclear.

Case records of 64 dogs with nasal adenocarcinoma were reviewed. The effects of age, gender, tumor stage, presence of metastatic lesions. and treatment method on survival time were examined. Surgery groups included rhinotomy (n = 9). transnasal curettage (n = 29). and no surgery (n = 26). Chemotherapy groups included fluorouracil-cyclophosphamide combination therapy (n = 1% mitoxantrone (n = 7). and no chemotherapy (n = 42). Fifty-three dogs received fractionated cobalt 60 radiation therapy. Surgical procedure. chemotherapy group. and stage of primary tumor were not significantly associated with survival time (P > .05). Dogs that received radiation therapy had a significantly longer median survival time (424 days) than dogs that did not (126 days) (P = .0001). The presence of either regional lymph node or pulmonary metastasis was associated with significantly shorter median survival time (109 days) when compared to dogs without metastases (393 days) ( P = .0125). When only dogs that had received radiation therapy were considered, neither surgical treatment nor chemotherapy group was associated with significant changes in median survival time. An alternate staging system emphasizing the presence or absence of metastases is proposed.Key words: Chemotherapy; Metastasis; Radiotherapy.umors of the nasal cavity and paranasal sinuses com-T prise less than 2% of canine neoplasms.' Most of these tumors are malignant and associated with a poor prognosis.l-3 Nasal carcinomas occur more frequently than sarcomas in all domestic species.I Of carcinomas, adenocarcinoma is the most common nasal tumor in the dog.' Treatment options include surgery, chemotherapy, and ortho-or megavoltage teletherapy, used singly, or as combination therapies. Radiotherapy is employed most commonly and has been reported to provide better clinical responses than surgery or chemotherapy alone6-x; however, results have been uniformly poor. Extensive disease and bony destruction often preclude effective treatment. Reported mean survival time without treatment was 5 months.' A median survival.time of 23 months with radiotherapy was reported in 1 study.7 Subsequent studies indicated median survival of 16.5 months or less.6.".1"In previous reports of nasal tumors in the dog, tumors were not staged and dogs with metastasis were excluded.',h,'o Failure to recognize or include animals with metastatic lesions thus limited the ability to examine tumor stage as a prognostic indicator. Furthermore, previous reports included multiple tumor type^^,^,^,^,^,^^ and considerable variation in radiation dose and t~p e .~.~ In an effort to more accurately determine the prognostic significance of tumor stage for dogs with nasal tumors, this study was limited to 1 tumor type for which complete staging was performed. The efficacy of surgery, chemotherapy, and radiation therapy in the treatment of nasal adenocarcinoma was examined.

The use of AT(1)RB decreased systemic vascular resistance and attenuated local expression of the renin-angiotensin system but did not prevent adverse LV chamber and cardiomyocyte remodeling. These results suggest that blockade of the AT(1) receptor does not improve LV remodeling and function in the early myocardial adaptive phase of MR.