O Canada - Canadian Contributions to Understanding of MH

By MHAUS President Henry Rosenberg, MD, CPE

Canadian Anesthesiologists Society

Like the American Society of Anesthesiologists, the Canadian Anesthesiologists Society holds an annual educational meeting for its members. This past June MHAUS exhibited at the Canadian meeting. This was the first time in many years that we elected to attend the Canadian meeting. The reasons for this are several.

 

For many years a Canadian Malignant Hyperthermia Association (MHA) provided information to patients and providers in Canada. However a few years ago the association no longer had the resources to continue operation and closed. As a result many who obtained information from the MHA began to access information from MHAUS. In addition a few of our hotline consultants either trained in Canada or are in active practice in that country.

 

There are other reasons for a close connection to Canada by MHAUS.

I was once told that Dr. R. A. Gordon Chairman of Anesthesiology at University of Toronto in the 1960s-70s suggested the term malignant hyperthermia (or hyperpyrexia) as the name of the syndrome that was describe in the early 1960s.

 

When the MH Registry was formed in the late 1980s, Canadian testing centers and Canadian anesthesiologists were involved in establishing the guiding principles for the Registry and contributed cases to it. Hence the Registry was called the North American MH Registry. Although at one point there were four biopsy centers for MH in Canada, at present only two are active. One in Ottawa and the other in Toronto. Clinicians and scientists from both of those centers continue to be involved in MH research and in working with patients and anesthesiologists.

 

As I have written previously MH is truly an international problem, not limited to any country or ethnic group. For example, we recently learned from a Google search of a death in the Philippines from MH. It has been one of my personal goals to share educational information about MH and provide support to patients and providers in all countries. Because of our close connection to Canada we thought it a good idea to reconnect with the Canadian anesthesiologists. Dianne Daugherty, MHAUSâ?? executive director, staffed our exhibit booth and distributed a great deal of information and discussed the concerns about MH in Canada. One anesthesiologist informed her that in his community in Ontario, MH is a regular occurrence because of a large population of MH susceptibles. Others expressed concern about having adequate amounts of Dantrium IV (dantrolene sodium for injection) in some of the smaller, rural hospitals and being adequately prepared to treat a crisis.

 

In an effort to reach out to the Anesthesiologists community we have written letters to the Chiefs of Anesthesiology of all the hospitals in Canada telling them about our educational programs and inviting them to become members of MHAUS. Although â??United Statesâ?? is in our title, MH knows no boundaries.

 

Also attending the conference were representatives of the company that makes Dantrium for the US and Canada as well as other countries, JHP Pharmaceuticals LLC, and their distributor of Dantrium in Canada, Methapharm, Inc. These companies are relatively new and are anxious to understand the needs of the Anesthesiology community in both countries as it relates to treating MH.

 

We hope to build on this new beginning and attend the Canadian Anesthesiologists Society meetings on a regular basis in order to help us begin to connect with MH patients and their families who live in Canada.

 

Those who are interested in MH should also know that Canadian anesthesiologists and scientists have made an enormous impact on the understanding of MH and informing the medical and lay community of the disorder.

 

Beverly Britt was an anesthesiologist in Toronto in the 1960s when she became interested in the syndrome after caring for an MH patient. She recognized how little was known about MH at the time and embarked on clinical and epidemiologic studies of the syndrome. She partnered with a well known Canadian pharmacologist, Werner Kalow (1917-2008), to develop and describe the muscle biopsy contracture test for MH. She also utilized the swine model of MH to better understand how MH might be triggered and the early signs of MH. She and her colleagues established the first biopsy center for MH testing in Toronto and helped create the MHA (The Canadian equivalent of MHAUS). The very first medical conference on MH, which I was fortunate to attend, was the First International Workshop on MH held in Toronto in 1971. The papers were subsequently published in book form which became a tremendous source of information about the laboratory findings as well as the clinical signs of MH. Beverly became an international figure for her many journal articles and books and the numerous talks and lectures on MH that she delivered all over the world. Even though she retired in 1996, the biopsy center continues its activities.

 

Not too many years after the first international workshop, another was held in Banff, Canada hosted by Dr. Keith Brownell of Calgary.

 

Other Canadian investigators contributed basic and clinical information concerning MH over the years including epidemiologic data on the prevalence of the syndrome in certain provinces of Canada.

 

With the dawning of the molecular genetic era in the late 1980s Dr. David MacLennanâ??s laboratory at the University of Toronto raced ahead to identify the ryanodine receptor gene as causal for MH. He and his colleagues identified a key mutation in swine that predicts MH susceptibility in that species. The studies were extended to humans and led to fundamental insights into MH and the other muscle disorder associated with the ryanodine receptor gene, central core disease. Over the years Dr. MacLennan and his collaborators have performed basic research in the structure of the ryanodine receptor and its function in normal patients and in MH patients. These studies lead directly first to a molecular genetic diagnostic test in pigs in order to identify animals that would be susceptible to stress induced MH an economic problem for pig breeders and then to the basis for genetic testing for MH and central core disease in humans. Obviously many other researchers around the world have contributed to development of the current DNA test for MH, but Dr. MacLennanâ??s lab led the way.

 

So, those of you who may be reading this blog in Canada or know anesthesiologists and MH susceptibles in that country, please let them know that MHAUS is interested in understanding their needs and is happy to provide education and support for patients and professionals.

 

A Partial List of Canadian Physicians and Scientists who Contributed to our Understanding of MH

(Apologies to those inadvertently omitted.)

• Greg Allen
• Mychelle Bachand
• Depak Bose
• Beverly Britt
• Keith Brownell
• Charles Cattran
• Daniel Chartrand
• R.A. Gordon
• Werner Kalow
• George Karpati
• Julian Loke
• David MacLennan
• Kevin Nolan
• Rein Paasuke
• Lena Patel

 

Dedicated Biopsy Center personnel

• Wanda Frodis ( Toronto)
• Mary Lou Crossan (Ottawa)